ATP synthase subunit delta, mitochondrial, also known as ATP synthase F1 subunit delta or F-ATPase delta subunit is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''ATP5F1D'' (formerly ''ATP5D'')

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. This gene encodes a subunit of mitochondrial

ATP synthase ATP synthase is an enzyme that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). ATP synthase is a molecular machine. The overall reaction catalyzed ...

. Mitochondrial

catalyzes ATP synthesis, utilizing an

electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts: * The chemical gradient, or difference in Concentration, solute concentration across ...

protons A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' ( elementary charge). Its mass is slightly less than the mass of a neutron and approximately times the mass of an electron (the pro ...

across the inner membrane during

oxidative phosphorylation Oxidative phosphorylation(UK , US : or electron transport-linked phosphorylation or terminal oxidation, is the metabolic pathway in which Cell (biology), cells use enzymes to Redox, oxidize nutrients, thereby releasing chemical energy in order ...

Structure

The ''ATP5F1D'' gene is located on the p arm of

chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 61.7 million base pairs, the building material of DNA. It is considered the most Gene density, gene-ri ...

at position 13.3 and it spans 3,075 base pairs. The ''ATP5F1D'' gene produces a 17.5 kDa protein composed of 168

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. The coded

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

is a subunit of the mitochondrial ATP synthase (Complex V), which is composed of two linked multi-subunit complexes: the soluble catalytic core, F₁, and the

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. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

-spanning component, F_o, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a

stoichiometry Stoichiometry () is the relationships between the masses of reactants and Product (chemistry), products before, during, and following chemical reactions. Stoichiometry is based on the law of conservation of mass; the total mass of reactants must ...

of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the delta subunit of the catalytic core.

Alternatively spliced Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

transcript variants encoding the same

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

have been identified. The structure of the protein has been known to resemble a '

lollipop A lollipop is a type of sugar candy usually consisting of hard candy mounted on a stick and intended for sucking or licking. Different informal terms are used in different places, including lolly, sucker and sticky-pop. Lollipops are avail ...

' structure due to the attachment of the F1 catalytic unit to the mitochondrial inner membrane by the F0 unit.

Function

This gene encodes a subunit of the mitochondrial

(Complex V) of the mitochondrial respiratory chain, which is necessary for the

catalysis Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

of ATP synthesis. Utilizing an electrochemical gradient of protons produced by

electron transport An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples this ...

complexes of the respiratory chain, the

synthase In biochemistry, a synthase is an enzyme that catalyses a synthesis process. Note that, originally, biochemical nomenclature distinguished synthetases and synthases. Under the original definition, synthases do not use energy from nucleoside trip ...

converts ADP into ATP across the inner membrane during

. F-type ATPases consist of two structural domains, F1 and F0, that contribute to

. The F1 domain contains an extramembranous catalytic core and the F0 domain contains the membrane proton channel linked by a central and a peripheral stalk. During catalysis, ATP turnover in the catalytic domain of F1 is coupled by a rotary mechanism of the central stalk subunits to proton transport. The encoded protein is a part of the complex F1 domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha3beta3 subunits leads to the

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

of ATP in three separate catalytic sites on the beta subunits.

Clinical significance

Mutations of ''ATP5F1D'' have been associated with childhood

mitochondrial disorders Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of ...

with

phenotypes In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological properti ...

such as episodic decompensations,

lactic acidosis Lactic acidosis refers to the process leading to the production of lactate by anaerobic metabolism. It increases hydrogen ion concentration tending to the state of acidemia or low pH. The result can be detected with high levels of lactate and lo ...

, and

hyperammonemia Hyperammonemia, or high ammonia levels, is a metabolic disturbance characterised by an excess of ammonia in the blood. Severe hyperammonemia is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammoni ...

accompanied by

ketoacidosis Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes i ...

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

. Biallelic

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

of c.245C>T and c.317T>G in ''ATP5F1D'' were shown to cause a

metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the ...

with such phenotypes due to mitochondrial dysfunction in two unrelated individuals. Mutations of ''ATP5F1D'' with decreased expression of the protein have also been found to result in synaptic dysfunction of the mitochondria that could play an essential role in

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...

(ALS) pathogenesis.

Interactions

Among the two components, CF1 - the catalytic core - and CF0 - the membrane proton channel of the F-type ATPase, ATP5F1D is associated with the catalytic core. The catalytic core is composed of five different subunits including alpha, beta, gamma, delta, and epsilon subunits. The protein has additional interactions with ATP5I, ATP5O, PUS1, NDUFB5, GTPBP6, ATP5L, ATP5J and others.

References

External links