HOME

TheInfoList




A mitochondrion (; ) is a double-
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes (outer coverings of cells or organelles that all ...
-bound
organelle In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, ...
found in most
eukaryotic Eukaryotes () are organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interact ...
organisms. Mitochondria generate most of the cell's supply of
adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. The study of the properti ...

adenosine triphosphate
(ATP), subsequently utilized as a source of
chemical energy Chemical energy is the energy of chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects th ...
, using the energy of
oxygen Oxygen is the chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the chemical elements In chemistry, an element is a pure substance consisting only of atoms that all have the same ...
released in
aerobic respiration Aerobic means "requiring Earth's atmosphere, air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Cellular respiration#Aerobic r ...
at the inner mitochondrial membrane. They were first discovered by
Albert von Kölliker Albert von Kölliker (born Rudolf Albert Kölliker'';'' 6 July 18172 November 1905) was a Switzerland, Swiss anatomist, physiologist, and Histology, histologist. Biography Albert Kölliker was born in Zurich, Switzerland. His early education wa ...
in 1880 in the voluntary muscles of insects. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase coined by Philip Siekevitz in a 1957 article of the same name. Some cells in some
multicellular organism A multicellular organism is an organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy (biol ...
s lack mitochondria (for example, mature mammalian
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

red blood cell
s). A large number of
unicellular organism A unicellular organism, also known as a single-celled organism, is an organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Org ...
s, such as
microsporidia Microsporidia are a group of spore-forming unicellular A unicellular organism, also known as a single-celled organism, is an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any indi ...
, parabasalids and
diplomonad The diplomonads (Greek for "two units") are a group of flagellate 's '' Artforms of Nature'', 1904 (''Giardia lamblia'') ('' Chlamydomonas'') A flagellate is a cell or organism with one or more whip-like Appendage, appendages called flagellum, ...
s, have reduced or transformed their mitochondria into other structures. One
eukaryote Eukaryotes () are organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interact ...

eukaryote
, ''
Monocercomonoides ''Monocercomonoides'' is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, including the principles that underlie such classification. The term may also ...
'', is known to have completely lost its mitochondria, and one multicellular organism, '''', is known to have retained mitochondrion-related organelles in association with a complete loss of their mitochondrial genome. Mitochondria are commonly between 0.75 and 3  μm in area, but vary considerably in size and structure. Unless specifically
stained A stain is a discoloration that can be clearly distinguished from the surface, material, or medium it is found upon. They are caused by the chemical or physical interaction of two dissimilar materials. Accidental staining may make material, mat ...
, they are not visible. In addition to supplying cellular energy, mitochondria are involved in other tasks, such as
signaling In signal processing Signal processing is an electrical engineering subfield that focuses on analysing, modifying, and synthesizing signals such as audio signal processing, sound, image processing, images, and scientific measurements. Sig ...
,
cellular differentiation Cellular differentiation is the process in which a cell changes from one cell type A cell type is a classification used to distinguish between morphologically or phenotypically distinct cell forms within a species In biology, a sp ...
, and
cell death Cell death is the event of a biological cell The cell (from Latin ''cella'', meaning "small room") is the basic structural, functional, and biological unit of all known organisms. Cells are the smallest units of life, and hence are often refe ...

cell death
, as well as maintaining control of the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication In , DNA replication is the of pro ...

cell cycle
and
cell growth Cell growth refers to an ''increase in the total mass Mass is both a property Property (''latin: Res Privata'') in the Abstract and concrete, abstract is what belongs to or with something, whether as an attribute or as a component of said ...
.
Mitochondrial biogenesis Mitochondrial biogenesis is the process by which cells increase mitochondria A mitochondrion (, plural mitochondria) is a double membrane-bound organelle found in most eukaryotic organisms. Some cells in some multicellular organisms lack mit ...
is in turn temporally coordinated with these cellular processes. Mitochondria have been implicated in several human disorders and conditions, such as
mitochondrial disease Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria A mitochondrion (, plural mitochondria) is a double membrane-bound organelle found in most eukaryotic organisms. Some cells in some multicellul ...
s,
cardiac dysfunction Heart failure (HF), also known as congestive heart failure (CHF), (congestive) cardiac failure (CCF), and decompensatio cordis, is when the heart is unable to pump sufficiently to maintain blood flow to meet the body tissue, body tissues' needs ...
, heart failure and
autism Autism is a developmental disorder Developmental disorders comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas. There are several ways of using this term. The most narro ...

autism
. The number of mitochondria in a cell can vary widely by
organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological me ...

organism
,
tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubitata'', a species of geometer mot ...
, and cell type. A mature red blood cell has no mitochondria, whereas a
liver cell The liver is an Organ (anatomy), organ of the digestive system only found in vertebrates which detoxification, detoxifies various metabolites, Protein biosynthesis, synthesizes proteins and produces biochemicals necessary for digestion and growt ...
can have more than 2000. The mitochondrion is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane,
intermembrane space #REDIRECT Intermembrane space#REDIRECT Intermembrane space The intermembrane space (IMS) is the space occurring between or involving two or more membranes. In cell biology, it is most commonly described as the region between the inner membrane and ...
, inner membrane,
crista A crista (; plural cristae) is a fold in the inner membrane of a mitochondrion A mitochondrion (; ) is a double-lipid bilayer, membrane-bound organelle found in most eukaryotic organisms. Mitochondria generate most of the Cell (biology), cell ...

crista
e and
matrix Matrix or MATRIX may refer to: Science and mathematics * Matrix (mathematics), a rectangular array of numbers, symbols, or expressions * Matrix (logic), part of a formula in prenex normal form * Matrix (biology), the material in between a eukaryoti ...
. Although most of a cell's
DNA Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neutral gro ...

DNA
is contained in the
cell nucleus In cell biology, the nucleus (pl. ''nuclei''; from Latin or , meaning ''kernel'' or ''seed'') is a biological membrane#Function, membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotes usually have a single n ...

cell nucleus
, the mitochondrion has ("mitogenome") that is substantially similar to
bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

bacteria
l genomes. Mitochondrial proteins (proteins transcribed from mitochondrial DNA) vary depending on the tissue and the species. In humans, 615 distinct types of proteins have been identified from
cardiac The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ...

cardiac
mitochondria, whereas in
rats Rats are various medium-sized, long-tailed rodent Rodents (from Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken in the area ar ...
, 940 proteins have been reported. The mitochondrial
proteome The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
is thought to be dynamically regulated.


Structure

Mitochondria may have a number of different shapes. A mitochondrion contains outer and inner membranes composed of
phospholipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane A polarized membrane is a lipid bilayer, lipid membrane that has a positive electrical charge on one side and a negative charge on another side, which produces the resting pote ...
s and
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

protein
s. The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion: # The outer mitochondrial membrane, # The intermembrane space (the space between the outer and inner membranes), # The inner mitochondrial membrane, # The
crista A crista (; plural cristae) is a fold in the inner membrane of a mitochondrion A mitochondrion (; ) is a double-lipid bilayer, membrane-bound organelle found in most eukaryotic organisms. Mitochondria generate most of the Cell (biology), cell ...

crista
e space (formed by infoldings of the inner membrane), and # The
matrix Matrix or MATRIX may refer to: Science and mathematics * Matrix (mathematics), a rectangular array of numbers, symbols, or expressions * Matrix (logic), part of a formula in prenex normal form * Matrix (biology), the material in between a eukaryoti ...
(space within the inner membrane), which is a fluid. Mitochondria have folding to increase surface area, which in turn increases ATP (Adenosine Tri Phosphate) production. Mitochondria stripped of their outer membrane are called
mitoplastA mitoplast is a mitochondrion that has been stripped of its inner mitochondrial membrane, outer membrane leaving the Inner mitochondrial membrane, inner membrane intact. In Electrophysiology Mitoplasts are useful for Electrophysiology, electroph ...
s.


Outer membrane

The outer mitochondrial membrane, which encloses the entire organelle, is 60 to 75
angstrom The angstromEntry "angstrom" in the Oxford online dictionary. Retrieved on 2019-03-02 from https://en.oxforddictionaries.com/definition/angstrom.Entry "angstrom" in the Merriam-Webster online dictionary. Retrieved on 2019-03-02 from https://www.m ...

angstrom
s (Å) thick. It has a protein-to-phospholipid ratio similar to that of the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...

cell membrane
(about 1:1 by weight). It contains large numbers of
integral membrane protein An integral membrane protein (IMP) is a type of membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. I ...
s called porins. A major trafficking protein is the pore-forming
voltage-dependent anion channel Voltage-dependent anion channels, or mitochondrial porins, are a class of porin (protein), porin ion channel located on the outer mitochondrial membrane. There is debate as to whether or not this channel is expressed in the cell surface membrane ...
(VDAC). The VDAC is the primary transporter of
nucleotide Nucleotides are organic molecules , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen chemical bond, bonds. Due to carbon's ability to Catenation, ...

nucleotide
s,
ion An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ...
s and
metabolite In biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, bio ...
s between the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a s ...
and the intermembrane space. It is formed as a
beta barrel In protein structures, a beta barrel is a beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected late ...
that spans the outer membrane, similar to that in the
gram-negative bacteria Gram-negative bacteria are bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), do ...
l membrane. Larger proteins can enter the mitochondrion if a signaling sequence at their
N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to hav ...

N-terminus
binds to a large multisubunit
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...
called translocase in the outer membrane, which then them across the membrane. Mitochondrial pro-proteins are imported through specialised translocation complexes. The outer membrane also contains
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s involved in such diverse activities as the elongation of
fatty acid In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...
s,
oxidation Redox (reduction–oxidation, pronunciation: or ) is a type of chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter ...

oxidation
of
epinephrine Adrenaline, also known as epinephrine, is a hormone A hormone (from the Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a co ...

epinephrine
, and the
degradation Degradation may refer to: Science * Degradation (geology), lowering of a fluvial surface by erosion * Degradation (telecommunications), of an electronic signal * Biodegradation of organic substances by living organisms * Environmental degradation i ...
of
tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a non-polar Aromatic hydrocarbon, aromatic amino ...

tryptophan
. These enzymes include
monoamine oxidase Monoamine oxidases (MAO) () are a family of enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing ...
,
rotenone Rotenone is an odorless, colorless, crystalline isoflavone used as a broad-spectrum insecticide, piscicide, and pesticide. It occurs naturally in the seeds and stems of several plants, such as the jicama vine plant, and the roots of several member ...

rotenone
-insensitive NADH-cytochrome c-reductase,
kynurenine -Kynurenine is a metabolite of the amino acid -tryptophan used in the production of niacin. Kynurenine is synthesized by the enzyme tryptophan dioxygenase, which is made primarily but not exclusively in the liver, and indoleamine 2,3-dioxygenase, ...

kynurenine
hydroxylase In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemistry, chemical process that introduces a hydroxyl group (-OH) into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH g ...
and fatty acid Co-A
ligase In biochemistry Biochemistry or biological chemistry, is the study of chemical process In a scientific Science () is a systematic enterprise that Scientific method, builds and organizes knowledge in the form of Testability, testable ...

ligase
. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to cell death. The outer mitochondrial membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and is involved in the transfer of lipids between the ER and mitochondria. Outside the outer membrane are small (diameter: 60 Å) particles named sub-units of Parson.


Intermembrane space

The mitochondrial intermembrane space is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules, such as ions and sugars, in the intermembrane space is the same as in the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a s ...
. However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a s ...
. One
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

protein
that is localized to the intermembrane space in this way is
cytochrome c The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion A mitochondrion (; ) is a double-membrane Image:Schematic size.jpg, up150px, Schematic of size-based membra ...

cytochrome c
.


Inner membrane

The inner mitochondrial membrane contains proteins with three types of functions: # Those that perform the
electron transport chain An electron transport chain (ETC) is a series of protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chain Peptides (from Greek language Greek (modern , romanized: ''Elliniká'', Anc ...

electron transport chain
redox Redox (reduction–oxidation, pronunciation: or ) is a type of chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substance A chemical substance is a form of matter ...

redox
reactions #
ATP synthase ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation of ...

ATP synthase
, which generates
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

ATP
in the matrix # Specific
transport proteins Transport (commonly used in the U.K.), or transportation (used in the U.S.), is the movement of humans, animals and goods In economics Economics () is the social science that studies how people interact with value; in particular, t ...
that regulate
metabolite In biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, bio ...
passage into and out of the
mitochondrial matrix In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondria's DNA, riboso ...
It contains more than 151 different
polypeptide Peptides (from Greek language Greek ( el, label=Modern Greek Modern Greek (, , or , ''Kiní Neoellinikí Glóssa''), generally referred to by speakers simply as Greek (, ), refers collectively to the dialects of the Greek language spoken ...
s, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion. Additionally, the inner membrane is rich in an unusual phospholipid,
cardiolipin Cardiolipin (IUPAC name 1,3-bis(''sn''-3’-phosphatidyl)-''sn''-glycerol) is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. It can also be found in the membranes of most ...

cardiolipin
. This phospholipid was originally discovered in
cow Cow is a colloquial term for cattle, and the name of female cattle. Cow, cows or COW may also refer to: Science and technology * Cow, an adult female of List of animal names, several animals * AT2018cow, a large astronomical explosion also kn ...
hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes. Cardiolipin contains four fatty acids rather than two, and may help to make the inner membrane impermeable. Unlike the outer membrane, the inner membrane does not contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the
translocase of the inner membrane The translocase of the inner membrane (TIM) is a complex of proteins found in the inner mitochondrial membrane of the mitochondria A mitochondrion (, plural mitochondria) is a double membrane-bound organelle found in most eukaryotic organis ...
(TIM) complex or via OXA1L. In addition, there is a membrane potential across the inner membrane, formed by the action of the
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s of the
electron transport chain An electron transport chain (ETC) is a series of protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chain Peptides (from Greek language Greek (modern , romanized: ''Elliniká'', Anc ...

electron transport chain
. Inner membrane fusion is mediated by the inner membrane protein
OPA1 Dynamin-like 120 kDa protein, mitochondrial is a protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions w ...
.


Cristae

The inner mitochondrial membrane is compartmentalized into numerous folds called
crista A crista (; plural cristae) is a fold in the inner membrane of a mitochondrion A mitochondrion (; ) is a double-lipid bilayer, membrane-bound organelle found in most eukaryotic organisms. Mitochondria generate most of the Cell (biology), cell ...

crista
e, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria, the area of the inner membrane is about five times as large as the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. Mitochondria within the same cell can have substantially different crista-density, with the ones that are required to produce more energy having much more crista-membrane surface. These folds are studded with small round bodies known as F particles or oxysomes.


Matrix

The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total proteins in a mitochondrion. The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, special mitochondrial
ribosomes Ribosomes () are molecular machine, macromolecular machines, found within all living cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order spec ...

ribosomes
,
tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an e ...

tRNA
, and several copies of the
mitochondrial DNA Mitochondrial DNA (mtDNA or mDNA) is the DNA Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five car ...

mitochondrial DNA
genome In the fields of molecular biology Molecular biology is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...

genome
. Of the enzymes, the major functions include oxidation of
pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid A carboxylic acid is an organic acid that contains a carboxyl group (C(=O)OH) attached to an R-group. The general formula of a carboxylic acid is R ...

pyruvate
and
fatty acids In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in ...
, and the
citric acid cycle The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle – is a series of chemical reactions to release stored energy through the redox, oxidation of acetyl-CoA derived from carbohydra ...

citric acid cycle
. The DNA molecules are packaged into nucleoids by proteins, one of which is
TFAM Mitochondrial transcription factor A, abbreviated as ''TFAM'' or ''mtTFA'', is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crysta ...
.


Function

The most prominent roles of mitochondria are to produce the energy currency of the cell,
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

ATP
(i.e., phosphorylation of ), through respiration and to regulate cellular
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life Life is a characteristic that distinguishes physical entities A bubble of exhaled gas in water In common usage and classical mechanics, a phys ...

metabolism
. The central set of reactions involved in ATP production are collectively known as the
citric acid cycle The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle – is a series of chemical reactions to release stored energy through the redox, oxidation of acetyl-CoA derived from carbohydra ...

citric acid cycle
, or the cycle. However, the mitochondrion has many other functions in addition to the production of ATP.


Energy conversion

A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of
glucose Glucose is a simple with the . Glucose is the most abundant , a subcategory of s. Glucose is mainly made by and most during from water and carbon dioxide, using energy from sunlight, where it is used to make in s, the most abundant carbohydr ...

glucose
:
pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid A carboxylic acid is an organic acid that contains a carboxyl group (C(=O)OH) attached to an R-group. The general formula of a carboxylic acid is R ...

pyruvate
, and
NADH Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate ...
, which are produced in the cytosol. This type of
cellular respiration Cellular respiration is a set of metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life Life is a characteristic that distinguishes physical entities that have biological processes, such a ...

cellular respiration
, known as
aerobic respiration Aerobic means "requiring Earth's atmosphere, air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Cellular respiration#Aerobic r ...
, is dependent on the presence of
oxygen Oxygen is the chemical element Image:Simple Periodic Table Chart-blocks.svg, 400px, Periodic table, The periodic table of the chemical elements In chemistry, an element is a pure substance consisting only of atoms that all have the same ...

oxygen
, which provides most of the energy released. When oxygen is limited, the glycolytic products will be metabolized by
anaerobic fermentation Fermentation is a metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life Life is a characteristic that distinguishes physical entities that have biological processes, such as signaling ...
, a process that is independent of the mitochondria. The production of ATP from glucose and oxygen has an approximately 13-times higher yield during aerobic respiration compared to fermentation. Plant mitochondria can also produce a limited amount of ATP either by breaking the sugar produced during photosynthesis or without oxygen by using the alternate substrate
nitrite The nitrite ion An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects tha ...

nitrite
. ATP crosses out through the inner membrane with the help of a specific protein, and across the outer membrane via porins. ADP returns via the same route.


Pyruvate and the citric acid cycle

Pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid A carboxylic acid is an organic acid that contains a carboxyl group (C(=O)OH) attached to an R-group. The general formula of a carboxylic acid is R ...

Pyruvate
molecules produced by
glycolysis Glycolysis is the metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of on ...

glycolysis
are across the inner mitochondrial membrane, and into the matrix where they can either be
oxidized (mild reducing agent) are added to powdered potassium permanganate (strong oxidizing agent), a violent redox reaction accompanied by self-ignition starts. Redox (reduction–oxidation, pronunciation: or ) is a type of chemical reaction A ...

oxidized
and combined with
coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...
to form CO,
acetyl-CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reaction Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organism In biology, an organism (from ...

acetyl-CoA
, and
NADH Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate ...
, or they can be carboxylated (by
pyruvate carboxylase Pyruvate carboxylase (PC) encoded by the gene PC is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate ...
) to form oxaloacetate. This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle and is therefore an anaplerotic reaction, increasing the cycle's capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g., in
muscle Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly cat ...

muscle
) are suddenly increased by activity. In the citric acid cycle, all the intermediates (e.g.
citrate Citric acid is an organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behav ...
, ,
alpha-ketoglutarate α-Ketoglutaric acid (2-oxoglutaric acid) is one of two ketone In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their ...

alpha-ketoglutarate
, succinate,
fumarate Fumaric acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297. The salts and esters are known as ...

fumarate
,
malate Malic acid is an organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavi ...
and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that the additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence, the addition of any one of them to the cycle has an anaplerotic effect, and its removal has a cataplerotic effect. These anaplerotic and cataplerotic reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid. This in turn increases or decreases the rate of
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

ATP
production by the mitochondrion, and thus the availability of ATP to the cell. Acetyl-CoA, on the other hand, derived from pyruvate oxidation, or from the
beta-oxidation 350px, Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, LCHAD deficiency In biochemistry an ...
of
fatty acids In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in ...
, is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO and water, with the energy thus released captured in the form of ATP. In the liver, the
carboxylationCarboxylation is a chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical A chemical substance is a form of matter having constant chem ...
of
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a s ...
ic pyruvate into intra-mitochondrial oxaloacetate is an early step in the pathway, which converts and de-aminated
alanine Alanine (symbol Ala or A) is an α-amino acid Amino acids are organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are ...

alanine
into glucose, under the influence of high levels of
glucagon Glucagon is a peptide hormonePeptide hormones or protein hormones are hormones whose molecules are peptides or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine ...

glucagon
and/or
epinephrine Adrenaline, also known as epinephrine, is a hormone A hormone (from the Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a co ...

epinephrine
in the blood. Here, the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate (malate) is immediately removed from the mitochondrion to be converted to cytosolic oxaloacetate, and ultimately to glucose, in a process that is almost the reverse of
glycolysis Glycolysis is the metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of on ...

glycolysis
. The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of
succinate dehydrogenase Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules up ...

succinate dehydrogenase
, which is bound to the inner mitochondrial membrane as part of Complex II. The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of
NADH Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate ...
and one molecule of
FADH In biochemistry Biochemistry or biological chemistry, is the study of es within and relating to living s. A sub-discipline of both and , biochemistry may be divided into three fields: , and . Over the last decades of the 20th century, b ...

FADH
) that are a source of electrons for the
electron transport chain An electron transport chain (ETC) is a series of protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chain Peptides (from Greek language Greek (modern , romanized: ''Elliniká'', Anc ...

electron transport chain
, and a molecule of GTP (which is readily converted to an ATP).


NADH and FADH: the electron transport chain

The electrons from NADH and FADH are transferred to oxygen (O), an energy-rich molecule, and hydrogen (protons) in several steps via the electron transport chain. NADH and FADH molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by
glycolysis Glycolysis is the metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of on ...

glycolysis
.
Reducing equivalent In biochemistry, the term reducing equivalent refers to any of a number of chemical species A chemical species is a chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substa ...
s from the cytoplasm can be imported via the
malate-aspartate shuttle The malate-aspartate shuttle (sometimes simply the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO−, and a ...

malate-aspartate shuttle
system of
antiporter An antiporter (also called exchanger or counter-transporter) is a cotransporterCotransporters are a subcategory of membrane transport protein A membrane transport protein (or simply transporter) is a membrane protein Membrane proteins are commo ...

antiporter
proteins or feed into the electron transport chain using a glycerol phosphate shuttle.
Protein complexes is a protein complex functioning as a molecular biological machine. It uses protein dynamics#Global_flexibility:_multiple_domains , protein domain dynamics on Nanoscopic scale, nanoscales A protein complex or multiprotein complex is a group of tw ...
in the inner membrane (
NADH dehydrogenase (ubiquinone) Respiratory complex I, (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial complex I) is the first large protein complex A protein complex or multiprotein complex is a group of two or more associated poly ...
,
cytochrome c reductaseCytochrome c reductase may refer to: * Coenzyme Q – cytochrome c reductase, an enzyme * NADH dehydrogenase, an enzyme {{Short pages monitor, paternal inheritance only occurs within males of the species. It has been suggested that it occurs at a very low level in humans. Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA. What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells. Further, evidence suggests that animal mitochondria can undergo recombination. The data are more controversial in humans, although indirect evidence of recombination exists. Entities undergoing uniparental inheritance and with little to no recombination may be expected to be subject to Muller's ratchet, the accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this buildup through a developmental process known as the Heteroplasmy#Mitochondrial bottleneck, mtDNA bottleneck. The bottleneck exploits cellular noise, stochastic processes in the cell to increase the cell-to-cell variability in heteroplasmy, mutant load as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo where different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilization or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated, with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mtDNA molecules within the cell.


DNA repair

Mitochondria can repair oxidative DNA damage (naturally occurring), DNA damage by mechanisms analogous to those occurring in the
cell nucleus In cell biology, the nucleus (pl. ''nuclei''; from Latin or , meaning ''kernel'' or ''seed'') is a biological membrane#Function, membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotes usually have a single n ...

cell nucleus
. The proteins employed in mitochondrial DNA, mtDNA repair are encoded by nuclear genes, and are translocated to the mitochondria. The DNA repair pathways in mammalian mitochondria include base excision repair, double-strand break repair, direct reversal and DNA mismatch repair, mismatch repair. Alternatively, DNA damage may be bypassed, rather than repaired, by translesion synthesis. Of the several DNA repair process in mitochondria, the base excision repair pathway has been most comprehensively studied. Base excision repair is carried out by a sequence of enzyme-catalyzed steps that include recognition and excision of a damaged DNA base, removal of the resulting abasic site, end processing, gap filling and ligation. A common damage in mtDNA that is repaired by base excision repair is 8-oxoguanine produced by oxidation of guanine. Double-strand breaks can be repaired by homologous recombinational repair in both mammalian mtDNA and plant mtDNA. Double-strand breaks in mtDNA can also be repaired by microhomology-mediated end joining. Although there is evidence for the repair processes of direct reversal and mismatch repair in mtDNA, these processes are not well characterized.


Lack of mitochondrial DNA

Some organisms have lost mitochondrial DNA altogether. In these cases, genes encoded by the mitochondrial DNA have been lost or transferred to the nucleus. ''Cryptosporidium'' have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred. In ''Cryptosporidium'', the mitochondria have an altered
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

ATP
generation system that renders the parasite resistant to many classical mitochondrial enzyme inhibitor, inhibitors such as cyanide, azide, and atovaquone. Mitochondria that lack their own DNA have been found in a marine parasitic dinoflagellate from the genus ''Amoebophyra''. This microorganism, ''A. cerati'', has functional mitochondria that lack a genome. In related species, the mitochondrial genome still has three genes, but in ''A. cerati'' only a single mitochondrial gene — the Cytochrome c oxidase subunit I, cytochrome c oxidase I gene (''cox1'') — is found, and it has migrated to the genome of the nucleus.


Population genetic studies

The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for studying population genetics and evolutionary biology. Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a phylogenetic tree, gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve. This is often interpreted as strong support for a recent modern human expansion Recent single-origin hypothesis, out of Africa. Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for the lack of interbreeding between Neanderthals and modern humans. However, mitochondrial DNA reflects only the history of the females in a population. This can be partially overcome by the use of paternal genetic sequences, such as the genetic recombination, non-recombining region of the Y-chromosome. Recent measurements of the molecular clock for mitochondrial DNA reported a value of 1 mutation every 7884 years dating back to the most recent common ancestor of humans and apes, which is consistent with estimates of mutation rates of autosomal DNA (10 per base per generation).


Dysfunction and disease


Mitochondrial diseases

Damage and subsequent dysfunction in mitochondria is an important factor in a range of human diseases due to their influence in cell metabolism. Mitochondrial disorders often present as neurological disorders, including
autism Autism is a developmental disorder Developmental disorders comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas. There are several ways of using this term. The most narro ...

autism
. They can also manifest as myopathy, diabetes, multiple endocrinopathy, and a variety of other systemic disorders. Diseases caused by mutation in the mtDNA include Kearns–Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy. In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. Diseases such as Kearns-Sayre syndrome, Pearson syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, MERRF syndrome, and others are due to point mutations in mtDNA. It has also been reported that drug tolerant cancer cells have an increased number and size of mitochondria which suggested an increase in mitochondrial biogenesis. Interestingly, a recent study in ''Nature Nanotechnology'' has reported that cancer cells can hijack the mitochondria from immune cells via physical tunneling nanotubes. In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease. These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome. Environmental influences may interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease. Other pathologies with etiology involving mitochondrial dysfunction include schizophrenia, bipolar disorder, dementia, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, cardiovascular disease, chronic fatigue syndrome, retinitis pigmentosa, and diabetes mellitus. Mitochondria-mediated oxidative stress plays a role in cardiomyopathy in type 2 diabetics. Increased fatty acid delivery to the heart increases fatty acid uptake by cardiomyocytes, resulting in increased fatty acid oxidation in these cells. This process increases the reducing equivalents available to the electron transport chain of the mitochondria, ultimately increasing reactive oxygen species (ROS) production. ROS increases uncoupling proteins (UCPs) and potentiate proton leakage through the adenine nucleotide translocator (ANT), the combination of which uncoupler, uncouples the mitochondria. Uncoupling then increases oxygen consumption by the mitochondria, compounding the increase in fatty acid oxidation. This creates a vicious cycle of uncoupling; furthermore, even though oxygen consumption increases, ATP synthesis does not increase proportionally because the mitochondria are uncoupled. Less ATP availability ultimately results in an energy deficit presenting as reduced cardiac efficiency and contractile dysfunction. To compound the problem, impaired sarcoplasmic reticulum calcium release and reduced mitochondrial reuptake limits peak cytosolic levels of the important signaling ion during muscle contraction. Decreased intra-mitochondrial calcium concentration increases dehydrogenase activation and ATP synthesis. So in addition to lower ATP synthesis due to fatty acid oxidation, ATP synthesis is impaired by poor calcium signaling as well, causing cardiac problems for diabetics.


Relationships to aging

There may be some leakage of the Electron transport chain, electrons transferred in the respiratory chain to form
reactive oxygen species Reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from O2. Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen (O2) produce ...
. This was thought to result in significant
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species Reactive oxygen species (ROS) are highly chemicals formed from O2. Examples of ROS include s, , , , and . The reduction of molecular oxygen ...
in the mitochondria with high mutation rates of mitochondrial DNA. Hypothesized links between aging and oxidative stress are not new and were proposed in 1956, which was later refined into the Mitochondrial theory of ageing, mitochondrial free radical theory of aging. A vicious cycle was thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress. A number of changes can occur to mitochondria during the aging process. Tissues from elderly humans show a decrease in enzymatic activity of the proteins of the respiratory chain. However, mutated mtDNA can only be found in about 0.2% of very old cells. Large deletions in the mitochondrial genome have been hypothesized to lead to high levels of
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species Reactive oxygen species (ROS) are highly chemicals formed from O2. Examples of ROS include s, , , , and . The reduction of molecular oxygen ...
and neuronal death in Parkinson's disease. Mitochondrial dysfunction has also been shown to occur in amyotrophic lateral sclerosis. Since mitochondria cover a pivotal role in the ovarian function, by providing ATP necessary for the development from germinal vesicle to mature oocyte, a decreased mitochondria function can lead to inflammation, resulting in premature ovarian failure and accelerated ovarian aging. The resulting dysfunction is then reflected in quantitative (such as mtDNA copy number and mtDNA deletions), qualitative (such as mutations and strand breaks) and oxidative damage (such as dysfunctional mitochondria due to ROS), which are not only relevant in ovarian aging, but perturb oocyte-cumulus crosstalk in the ovary, are linked to genetic disorders (such as Fragile X) and can interfere with embryo selection.


History

The first observations of intracellular structures that probably represented mitochondria were published in the 1840s. Richard Altmann, in 1890, established them as cell organelles and called them "bioblasts". In 1898, Carl Benda coined the term "mitochondria" from the Greek language, Greek , , "thread", and , , "granule". Leonor Michaelis discovered that Janus green can be used as a supravital stain for mitochondria in 1900. In 1904, Friedrich Meves, made the first recorded observation of mitochondria in plants in cells of the white waterlily, ''Nymphaea alba'' and in 1908, along with Claudius Regaud, suggested that they contain proteins and lipids. Benjamin F. Kingsbury, in 1912, first related them with cell respiration, but almost exclusively based on morphological observations. In 1913, particles from extracts of guinea-pig liver were linked to respiration by Otto Heinrich Warburg, which he called "grana". Warburg and Heinrich Otto Wieland, who had also postulated a similar particle mechanism, disagreed on the chemical nature of the respiration. It was not until 1925, when David Keilin discovered cytochromes, that the respiratory chain was described. In 1939, experiments using minced muscle cells demonstrated that cellular respiration using one Oxygen, oxygen molecule can form four
adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains with other carbon s), millions of organic compounds are known. The study of the properti ...

adenosine triphosphate
(ATP) molecules, and in 1941, the concept of the phosphate bonds of ATP being a form of energy in cellular metabolism was developed by Fritz Albert Lipmann. In the following years, the mechanism behind cellular respiration was further elaborated, although its link to the mitochondria was not known. The introduction of Cell fractionation, tissue fractionation by Albert Claude allowed mitochondria to be isolated from other cell fractions and biochemical analysis to be conducted on them alone. In 1946, he concluded that cytochrome oxidase and other enzymes responsible for the respiratory chain were isolated to the mitochondria. Eugene P. Kennedy, Eugene Kennedy and Albert L. Lehninger, Albert Lehninger discovered in 1948 that mitochondria are the site of oxidative phosphorylation in eukaryotes. Over time, the fractionation method was further developed, improving the quality of the mitochondria isolated, and other elements of Cellular respiration, cell respiration were determined to occur in the mitochondria. The first high-resolution electron micrographs appeared in 1952, replacing the Janus Green stains as the preferred way to visualize mitochondria. This led to a more detailed analysis of the structure of the mitochondria, including confirmation that they were surrounded by a membrane. It also showed a second membrane inside the mitochondria that folded up in ridges dividing up the inner chamber and that the size and shape of the mitochondria varied from cell to cell. The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957. In 1967, it was discovered that mitochondria contained
ribosomes Ribosomes () are molecular machine, macromolecular machines, found within all living cell (biology), cells, that perform Translation (biology), biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order spec ...

ribosomes
. In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA completed in 1976.


See also

* Anti-mitochondrial antibodies * Respirometry#Mitochondrial metabolic rates, Mitochondrial metabolic rates * Mitochondrial permeability transition pore * Mitophagy * Nebenkern * Oncocyte * Oncocytoma * Paternal mtDNA transmission * Plastid * Submitochondrial particle


References

General *


External links

*
Mitodb.com
– The mitochondrial disease database.

at University of Mainz
Mitochondria Research Portal
at mitochondrial.net

at cytochemistry.net

at University of Alabama
MIP
Mitochondrial Physiology Society
3D structures of proteins from inner mitochondrial membrane
at University of Michigan
3D structures of proteins associated with outer mitochondrial membrane
at University of Michigan
Mitochondrial Protein Partnership
at University of Wisconsin
MitoMiner – A mitochondrial proteomics database
at MRC Mitochondrial Biology Unit
Mitochondrion – Cell Centered Database


at San Diego State University
Video Clip of Rat-liver Mitochondrion from Cryo-electron Tomography
{{Authority control Mitochondria Cellular respiration Endosymbiotic events