Cytosolic DNA Sensor
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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: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the
mitochondrion A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which also comprises the mitochondria,
plastid The plastid (Greek: πλαστός; plastós: formed, molded – plural plastids) is a membrane-bound organelle found in the Cell (biology), cells of plants, algae, and some other eukaryotic organisms. They are considered to be intracellular endosy ...
s, and other
organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
s (but not their internal fluids and structures); the
cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
is separate. The cytosol is thus a liquid matrix around the organelles. In
prokaryotes A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles. The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and properties within cells is not well understood. The concentrations of ions such as sodium and potassium in the cytosol are different to those in the extracellular fluid; these differences in ion levels are important in processes such as osmoregulation, cell signaling, and the generation of action potentials in excitable cells such as endocrine, nerve and muscle cells. The cytosol also contains large amounts of
macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
s, which can alter how molecules behave, through macromolecular crowding. Although it was once thought to be a simple solution of molecules, the cytosol has multiple levels of organization. These include
concentration gradient Molecular diffusion, often simply called diffusion, is the thermal motion of all (liquid or gas) particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size (mass) of ...
s of small molecules such as calcium, large complexes of enzymes that act together and take part in metabolic pathways, and protein complexes such as
proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by w ...
s and carboxysomes that enclose and separate parts of the cytosol.


Definition

The term "cytosol" was first introduced in 1965 by H. A. Lardy, and initially referred to the liquid that was produced by breaking cells apart and pelleting all the insoluble components by ultracentrifugation. Such a soluble cell extract is not identical to the soluble part of the cell cytoplasm and is usually called a cytoplasmic fraction. The term ''cytosol'' is now used to refer to the liquid phase of the cytoplasm in an intact cell. This excludes any part of the cytoplasm that is contained within organelles. Due to the possibility of confusion between the use of the word "cytosol" to refer to both extracts of cells and the soluble part of the cytoplasm in intact cells, the phrase "aqueous cytoplasm" has been used to describe the liquid contents of the cytoplasm of living cells. Prior to this, other terms, including hyaloplasm, were used for the cell fluid, not always synonymously, as its nature was not very clear (see
protoplasm Protoplasm (; ) is the living part of a cell that is surrounded by a plasma membrane. It is a mixture of small molecules such as ions, monosaccharides, amino acid, and macromolecules such as proteins, polysaccharides, lipids, etc. In some defini ...
).


Properties and composition

The proportion of cell volume that is cytosol varies: for example while this compartment forms the bulk of cell structure in bacteria, in plant cells the main compartment is the large central vacuole. The cytosol consists mostly of water, dissolved ions, small molecules, and large water-soluble molecules (such as proteins). The majority of these non-protein molecules have a molecular mass of less than 300  Da. This mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism (the
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s) is immense. For example, up to 200,000 different small molecules might be made in plants, although not all these will be present in the same species, or in a single cell. Estimates of the number of metabolites in single cells such as ''
E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' and baker's yeast predict that under 1,000 are made.


Water

Most of the cytosol is water, which makes up about 70% of the total volume of a typical cell. The pH of the intracellular fluid is 7.4. while human cytosolic pH ranges between 7.0–7.4, and is usually higher if a cell is growing. The viscosity of cytoplasm is roughly the same as pure water, although diffusion of small molecules through this liquid is about fourfold slower than in pure water, due mostly to collisions with the large numbers of
macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
s in the cytosol. Studies in the brine shrimp have examined how water affects cell functions; these saw that a 20% reduction in the amount of water in a cell inhibits metabolism, with metabolism decreasing progressively as the cell dries out and all metabolic activity halting when the water level reaches 70% below normal. Although water is vital for life, the structure of this water in the cytosol is not well understood, mostly because methods such as nuclear magnetic resonance spectroscopy only give information on the average structure of water, and cannot measure local variations at the microscopic scale. Even the structure of pure water is poorly understood, due to the ability of water to form structures such as
water cluster In chemistry, a water cluster is a discrete hydrogen bonded assembly or cluster of molecules of water. Many such clusters have been predicted by theoretical models ( in silico), and some have been detected experimentally in various contexts suc ...
s through
hydrogen bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
s. The classic view of water in cells is that about 5% of this water is strongly bound in by solutes or macromolecules as water of solvation, while the majority has the same structure as pure water. This water of solvation is not active in osmosis and may have different solvent properties, so that some dissolved molecules are excluded, while others become concentrated. However, others argue that the effects of the high concentrations of macromolecules in cells extend throughout the cytosol and that water in cells behaves very differently from the water in dilute solutions. These ideas include the proposal that cells contain zones of low and high-density water, which could have widespread effects on the structures and functions of the other parts of the cell. However, the use of advanced nuclear magnetic resonance methods to directly measure the mobility of water in living cells contradicts this idea, as it suggests that 85% of cell water acts like that pure water, while the remainder is less mobile and probably bound to macromolecules.


Ions

The concentrations of the other ions in cytosol are quite different from those in extracellular fluid and the cytosol also contains much higher amounts of charged macromolecules such as proteins and nucleic acids than the outside of the cell structure. In contrast to extracellular fluid, cytosol has a high concentration of potassium ions and a low concentration of sodium ions. This difference in ion concentrations is critical for osmoregulation, since if the ion levels were the same inside a cell as outside, water would enter constantly by osmosis - since the levels of
macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
s inside cells are higher than their levels outside. Instead, sodium ions are expelled and potassium ions taken up by the Na⁺/K⁺-ATPase, potassium ions then flow down their concentration gradient through potassium-selection ion channels, this loss of positive charge creates a negative
membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
. To balance this potential difference, negative chloride ions also exit the cell, through selective chloride channels. The loss of sodium and chloride ions compensates for the osmotic effect of the higher concentration of organic molecules inside the cell. Cells can deal with even larger osmotic changes by accumulating osmoprotectants such as
betaines A betaine () in chemistry is any neutral chemical compound with a positively charged cationic functional group, such as a quaternary ammonium or phosphonium cation (generally: onium ions) that bears no hydrogen atom and with a negatively charged f ...
or trehalose in their cytosol. Some of these molecules can allow cells to survive being completely dried out and allow an organism to enter a state of suspended animation called
cryptobiosis Cryptobiosis or anabiosis is a metabolic state of life entered by an organism in response to adverse environmental conditions such as desiccation, freezing, and oxygen deficiency. In the cryptobiotic state, all measurable metabolic processes stop ...
. In this state the cytosol and osmoprotectants become a glass-like solid that helps stabilize proteins and cell membranes from the damaging effects of desiccation. The low concentration of calcium in the cytosol allows calcium ions to function as a
second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
in calcium signaling. Here, a signal such as a hormone or an action potential opens
calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables e ...
so that calcium floods into the cytosol. This sudden increase in cytosolic calcium activates other signalling molecules, such as
calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...
and
protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
. Other ions such as chloride and potassium may also have signaling functions in the cytosol, but these are not well understood.


Macromolecules

Protein molecules that do not bind to cell membranes or the cytoskeleton are dissolved in the cytosol. The amount of protein in cells is extremely high, and approaches 200 mg/ml, occupying about 20–30% of the volume of the cytosol. However, measuring precisely how much protein is dissolved in cytosol in intact cells is difficult, since some proteins appear to be weakly associated with membranes or organelles in whole cells and are released into solution upon cell lysis. Indeed, in experiments where the plasma membrane of cells were carefully disrupted using
saponin Saponins (Latin "sapon", soap + "-in", one of), also selectively referred to as triterpene glycosides, are bitter-tasting usually toxic plant-derived organic chemicals that have a foamy quality when agitated in water. They are widely distributed ...
, without damaging the other cell membranes, only about one quarter of cell protein was released. These cells were also able to synthesize proteins if given ATP and amino acids, implying that many of the enzymes in cytosol are bound to the cytoskeleton. However, the idea that the majority of the proteins in cells are tightly bound in a network called the
microtrabecular lattice The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compo ...
is now seen as unlikely. In prokaryotes the cytosol contains the cell's genome, within a structure known as a
nucleoid The nucleoid (meaning ''nucleus-like'') is an irregularly shaped region within the prokaryotic cell that contains all or most of the genetic material. The chromosome of a prokaryote is circular, and its length is very large compared to the cell dim ...
. This is an irregular mass of DNA and associated proteins that control the
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
and
replication Replication may refer to: Science * Replication (scientific method), one of the main principles of the scientific method, a.k.a. reproducibility ** Replication (statistics), the repetition of a test or complete experiment ** Replication crisi ...
of the bacterial chromosome and
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s. In eukaryotes the genome is held within the
cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
, which is separated from the cytosol by nuclear pores that block the free diffusion of any molecule larger than about 10 
nanometre 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
s in diameter. This high concentration of macromolecules in cytosol causes an effect called macromolecular crowding, which is when the effective concentration of other macromolecules is increased, since they have less volume to move in. This crowding effect can produce large changes in both the
rates Rate or rates may refer to: Finance * Rates (tax), a type of taxation system in the United Kingdom used to fund local government * Exchange rate, rate at which one currency will be exchanged for another Mathematics and science * Rate (mathema ...
and the position of chemical equilibrium of reactions in the cytosol. It is particularly important in its ability to alter
dissociation constant In chemistry, biochemistry, and pharmacology, a dissociation constant (K_D) is a specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex fa ...
s by favoring the association of macromolecules, such as when multiple proteins come together to form protein complexes, or when DNA-binding proteins bind to their targets in the genome.


Organization

Although the components of the cytosol are not separated into regions by cell membranes, these components do not always mix randomly and several levels of organization can localize specific molecules to defined sites within the cytosol.


Concentration gradients

Although small molecules diffuse rapidly in the cytosol, concentration gradients can still be produced within this compartment. A well-studied example of these are the "calcium sparks" that are produced for a short period in the region around an open
calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables e ...
. These are about 2  micrometres in diameter and last for only a few
millisecond A millisecond (from '' milli-'' and second; symbol: ms) is a unit of time in the International System of Units (SI) equal to one thousandth (0.001 or 10−3 or 1/1000) of a second and to 1000 microseconds. A unit of 10 milliseconds may be called ...
s, although several sparks can merge to form larger gradients, called "calcium waves". Concentration gradients of other small molecules, such as oxygen and adenosine triphosphate may be produced in cells around clusters of
mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, although these are less well understood.


Protein complexes

Proteins can associate to form protein complexes, these often contain a set of proteins with similar functions, such as enzymes that carry out several steps in the same metabolic pathway. This organization can allow substrate channeling, which is when the product of one enzyme is passed directly to the next enzyme in a pathway without being released into solution. Channeling can make a pathway more rapid and efficient than it would be if the enzymes were randomly distributed in the cytosol, and can also prevent the release of unstable reaction intermediates. Although a wide variety of metabolic pathways involve enzymes that are tightly bound to each other, others may involve more loosely associated complexes that are very difficult to study outside the cell. Consequently, the importance of these complexes for metabolism in general remains unclear.


Protein compartments

Some protein complexes contain a large central cavity that is isolated from the remainder of the cytosol. One example of such an enclosed compartment is the
proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by w ...
. Here, a set of subunits form a hollow barrel containing proteases that degrade cytosolic proteins. Since these would be damaging if they mixed freely with the remainder of the cytosol, the barrel is capped by a set of regulatory proteins that recognize proteins with a signal directing them for degradation (a ubiquitin tag) and feed them into the proteolytic cavity. Another large class of protein compartments are
bacterial microcompartments Bacterial microcompartments (BMCs) are organelle-like structures found in bacteria. They consist of a protein shell that encloses enzymes and other proteins. BMCs are typically about 40–200 nanometers in diameter and are made entirely of prote ...
, which are made of a protein shell that encapsulates various enzymes. These compartments are typically about 100–200
nanometre 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
s across and made of interlocking proteins. A well-understood example is the carboxysome, which contains enzymes involved in
carbon fixation Biological carbon fixation or сarbon assimilation is the process by which inorganic carbon (particularly in the form of carbon dioxide) is converted to organic compounds by living organisms. The compounds are then used to store energy and as ...
such as RuBisCO.


Biomolecular condensates

Non-membrane bound organelles can form as biomolecular condensates, which arise by clustering, oligomerisation, or polymerisation of macromolecules to drive
colloid A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others extend ...
al phase separation of the cytoplasm or nucleus.


Cytoskeletal sieving

Although the cytoskeleton is not part of the cytosol, the presence of this network of filaments restricts the diffusion of large particles in the cell. For example, in several studies tracer particles larger than about 25 
nanometre 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
s (about the size of a
ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
) were excluded from parts of the cytosol around the edges of the cell and next to the nucleus. These "excluding compartments" may contain a much denser meshwork of actin fibres than the remainder of the cytosol. These microdomains could influence the distribution of large structures such as
ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
s and organelles within the cytosol by excluding them from some areas and concentrating them in others.


Function

The cytosol is the site of multiple cell processes. Examples of these processes include
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
from the cell membrane to sites within the cell, such as the
cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
, or organelles. This compartment is also the site of many of the processes of cytokinesis, after the breakdown of the nuclear membrane in
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
. Another major function of cytosol is to transport metabolites from their site of production to where they are used. This is relatively simple for water-soluble molecules, such as amino acids, which can diffuse rapidly through the cytosol. However, hydrophobic molecules, such as fatty acids or
sterol Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...
s, can be transported through the cytosol by specific binding proteins, which shuttle these molecules between cell membranes. Molecules taken into the cell by
endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
or on their way to be secreted can also be transported through the cytosol inside
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
, which are small spheres of lipids that are moved along the cytoskeleton by
motor protein Motor proteins are a class of molecular motors that can move along the cytoplasm of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump. Cellular functions ...
s. The cytosol is the site of most metabolism in prokaryotes, and a large proportion of the metabolism of eukaryotes. For instance, in mammals about half of the proteins in the cell are localized to the cytosol. The most complete data are available in yeast, where metabolic reconstructions indicate that the majority of both metabolic processes and metabolites occur in the cytosol. Major metabolic pathways that occur in the cytosol in animals are
protein biosynthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical ...
, the pentose phosphate pathway,
glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
and
gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
. The localization of pathways can be different in other organisms, for instance fatty acid synthesis occurs in
chloroplast A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it in ...
s in plants and in
apicoplast An apicoplast is a Synapomorphy, derived non-photosynthetic plastid found in most Apicomplexa, including ''Toxoplasma gondii'', and ''Plasmodium falciparum'' and other ''Plasmodium'' spp. (parasites causing malaria), but not in others such as ''Cry ...
s in apicomplexa.


References


Further reading

* {{Good article Cell anatomy Cytoplasm