Editing Cytosol

{{Short description|Liquid found in cells}}
[[Image:Crowded cytosol.png|thumb|right|300px|The cytosol is a crowded solution of many different types of molecules that occupy up to 30% of the cytoplasmic volume.<ref name="Ellis-2001" />]]
{{Organelle diagram|300px}}

The '''cytosol''', also known as '''cytoplasmic matrix''' or '''groundplasm''',<ref name="Cammack-2006b">{{cite web |last1=Cammack |first1=Richard|last2=Atwood |first2=Teresa|last3=Campbell |first3=Peter|last4=Parish |first4=Howard|last5=Smith |first5=Anthony|last6=Vella |first6=Frank|last7=Stirling |first7=John|editor7-first=John |editor7-last=Stirling |editor6-first=Frank |editor6-last=Vella |editor5-first=Anthony |editor5-last=Smith |editor4-first=Howard |editor4-last=Parish |editor3-first=Peter |editor3-last=Campbell |editor2-first=Teresa |editor2-last=Atwood |editor1-first=Richard |editor1-last=Cammack |title=Cytoplasmic matrix |url=http://www.oxfordreference.com/abstract/10.1093/acref/9780198529170.001.0001/acref-9780198529170-e-4665?rskey=4btyut&result=3 |website=Oxford Dictionary of Biochemistry and Molecular Biology |publisher=Oxford University Press |language=en |doi=10.1093/acref/9780198529170.001.0001 |date=2006|isbn=9780198529170 }}</ref> is one of the liquids found inside cells ([[Fluid compartments#Intracellular compartment|intracellular fluid]] (ICF)).<ref name="Liachovitzky-2015">{{Cite journal|url=https://academicworks.cuny.edu/bx_oers/1/|title=Human Anatomy and Physiology Preparatory Course|access-date=2021-06-22|journal=Open Educational Resources|last=Liachovitzky|first=Carlos|archive-url=https://web.archive.org/web/20170823135557/http://academicworks.cuny.edu/bx_oers/1/|archive-date=2017-08-23|url-status=live|publisher=CUNY Academic Works|year=2015|page=69|format=pdf}}</ref> It is separated into compartments by membranes. For example, the [[mitochondrial matrix]] separates the mitochondrion 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]]s, and other [[organelle]]s (but not their internal fluids and structures); the [[cell nucleus]] is separate. The cytosol is thus a liquid matrix around the organelles. In [[prokaryotes]], 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 pathway]]s 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 [[ion]]s 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]]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 [[diffusion|concentration gradient]]s of small molecules such as [[calcium]], large complexes of [[enzyme]]s that act together and take part in [[metabolic pathway]]s, and [[protein complex]]es such as [[proteasome]]s and [[carboxysome]]s 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 [[Ultracentrifuge|ultracentrifugation]].<ref>Lardry, H. A. 1969. On the direction of pyridine nucleotide oxidation-reduction reactions in gluconeogenesis and lipogenesis. In: ''Control of energy metabolism'', edited by B. Chance, R. Estabrook, and J. R. Williamson. New York: Academic, 1965, p. 245, [https://books.google.com/books?id=MUueBQAAQBAJ].</ref><ref name="James-1984"/> Such a soluble cell extract is not identical to the soluble part of the cell cytoplasm and is usually called a cytoplasmic fraction.<ref name="Cammack-2006"/>

The term ''cytosol'' is now used to refer to the liquid phase of the cytoplasm in an intact cell.<ref name="Cammack-2006">{{cite book |author1=Cammack, Richard |author2=Teresa Atwood |author3=Attwood, Teresa K. |author4=Campbell, Peter Scott |author5=Parish, Howard I. |author6=Smith, Tony |author7=Vella, Frank |author8=Stirling, John |title=Oxford dictionary of biochemistry and molecular biology |publisher=Oxford University Press |location=Oxford [Oxfordshire] |year=2006 |isbn=0-19-852917-1 |oclc=225587597}}</ref> This excludes any part of the cytoplasm that is contained within organelles.<ref name="Lodish-1999"/> 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.<ref name="James-1984"/>

Prior to this, other terms, including '''hyaloplasm''',<ref>Hanstein, J. (1880). ''[https://archive.org/details/DasProtoplasma Das Protoplasma]''. Heidelberg. p. 24.</ref> were used for the cell fluid, not always synonymously, as its nature was not well understood (see [[protoplasm]]).<ref name="Cammack-2006"/>

==Properties and composition==
[[File:Cellular Fluid Content.jpg|thumb|Intracellular fluid content in humans]]
The proportion of cell volume that is cytosol varies: for example while this compartment forms the bulk of cell structure in [[bacteria]],<ref name="Hoppert-1999"/> in plant cells the main compartment is the large central [[vacuole]].<ref>{{cite journal |vauthors=Bowsher CG, Tobin AK |title=Compartmentation of metabolism within mitochondria and plastids |journal=J. Exp. Bot. |volume=52 |issue=356 |pages=513–27 |date=April 2001 |pmid=11373301 |doi=10.1093/jexbot/52.356.513 |doi-access=free }}</ref> 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&nbsp;[[Atomic mass unit|Da]].<ref>{{cite journal |vauthors=Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB |title=Metabolomics by numbers: acquiring and understanding global metabolite data |journal=Trends Biotechnol. |volume=22 |issue=5 |pages=245–52 |date=May 2004 |pmid=15109811 |doi=10.1016/j.tibtech.2004.03.007 |url=http://personalpages.manchester.ac.uk/staff/roy.goodacre/learning/metabprof/Goodacre-TibTech2004.pdf |url-status=dead |archive-url=https://web.archive.org/web/20081217001301/http://personalpages.manchester.ac.uk/staff/roy.goodacre/learning/metabprof/Goodacre-TibTech2004.pdf |archive-date=2008-12-17 }}</ref> This mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism (the [[metabolite]]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.<ref>{{cite journal |author=Weckwerth W |s2cid=1197884 |title=Metabolomics in systems biology |journal=[[Annu Rev Plant Biol]] |volume=54 |pages=669–89 |year=2003 |pmid=14503007 |doi=10.1146/annurev.arplant.54.031902.135014}}</ref> Estimates of the number of metabolites in single cells such as ''[[Escherichia coli|E. coli]]'' and [[Saccharomyces cerevisiae|baker's yeast]] predict that under 1,000 are made.<ref>{{cite journal |vauthors=Reed JL, Vo TD, Schilling CH, Palsson BO |title=An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR) |journal=Genome Biol. |volume=4 |issue=9 |pages=R54 |year=2003 |pmid=12952533 |pmc=193654 |doi=10.1186/gb-2003-4-9-r54 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Förster J, Famili I, Fu P, Palsson BØ, Nielsen J |title=Genome-Scale Reconstruction of the Saccharomyces cerevisiae Metabolic Network |journal=Genome Res. |volume=13 |issue=2 |pages=244–53 |date=February 2003 |pmid=12566402 |pmc=420374 |doi=10.1101/gr.234503 }}</ref>

===Water===
Most of the cytosol is  [[water]], which makes up about 70% of the total volume of a typical cell.<ref name="Luby-Phelps-2000">{{cite journal |author=Luby-Phelps K |title=Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area |journal=Int. Rev. Cytol. |volume=192 |pages=189–221 |year=2000 |pmid=10553280 |doi=10.1016/S0074-7696(08)60527-6 |url=http://webusers.physics.illinois.edu/~alek/598PNM/hw/IntRevCytol.pdf |series=International Review of Cytology |isbn=978-0-12-364596-8 |url-status=dead |archive-url=https://web.archive.org/web/20110719211202/http://webusers.physics.illinois.edu/~alek/598PNM/hw/IntRevCytol.pdf |archive-date=2011-07-19 }}</ref> The [[intracellular pH|pH]] of the intracellular fluid is 7.4.<ref>{{cite journal |vauthors=Roos A, Boron WF |title=Intracellular pH |journal=Physiol. Rev. |volume=61 |issue=2 |pages=296–434 |date=April 1981 |pmid=7012859 |doi=10.1152/physrev.1981.61.2.296 }}</ref> while mouse cell cytosolic [[pH]] ranges between 7.0 and 7.4, and is usually higher if a cell is growing.<ref>{{Cite journal| pmid = 3558476| volume = 104| issue = 4| pages = 1019–1033| last1 = Bright| first1 = G R| title = Fluorescence ratio imaging microscopy: temporal and spatial measurements of cytoplasmic pH| journal = The Journal of Cell Biology| year = 1987| doi = 10.1083/jcb.104.4.1019| last2 = Fisher| first2 = GW| last3 = Rogowska| first3 = J| last4 = Taylor| first4 = DL| pmc = 2114443}}</ref> 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]]s in the cytosol.<ref name="Verkman-2002">{{cite journal |author=Verkman AS |title=Solute and macromolecule diffusion in cellular aqueous compartments |journal=Trends Biochem. Sci. |volume=27 |issue=1 |pages=27–33 |date=January 2002 |pmid=11796221 |doi=10.1016/S0968-0004(01)02003-5}}</ref> 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.<ref name="James-1984">{{cite journal |author=Clegg James S. |author-link = James S. Clegg|title=Properties and metabolism of the aqueous cytoplasm and its boundaries |journal=Am. J. Physiol. |volume=246 |issue=2 Pt 2 |pages=R133–51 |date=1984 |pmid=6364846 |doi=10.1152/ajpregu.1984.246.2.R133 | s2cid=30351411 |doi-access=}}</ref>

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]]s through [[hydrogen bond]]s.<ref name="Wiggins-1990"/>

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.<ref name="James-1984"/> 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.<ref>{{cite journal |author=Fulton AB |title=How crowded is the cytoplasm? |journal=Cell |volume=30 |issue=2 |pages=345–7 |date=September 1982 |pmid=6754085 |doi=10.1016/0092-8674(82)90231-8|s2cid=6370250 }}</ref><ref>{{cite journal |author=Garlid KD |title=The state of water in biological systems |journal=Int. Rev. Cytol. |volume=192 |pages=281–302 |year=2000 |pmid=10553283 |doi=10.1016/S0074-7696(08)60530-6 |series=International Review of Cytology |isbn=978-0-12-364596-8}}</ref> 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.<ref>{{cite journal |author=Chaplin M |title=Do we underestimate the importance of water in cell biology? |journal=Nat. Rev. Mol. Cell Biol. |volume=7 |issue=11 |pages=861–6 |date=November 2006 |pmid=16955076 |doi=10.1038/nrm2021|s2cid=42919563 }}</ref> 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.<ref name="Wiggins-1990">{{cite journal|author=Wiggins PM|author-link=Philippa Wiggins|date=1 December 1990|title=Role of water in some biological processes|journal=Microbiol. Rev.|volume=54|issue=4|pages=432–49|doi=10.1128/MMBR.54.4.432-449.1990|pmc=372788|pmid=2087221}}</ref><ref>{{cite journal|author=Wiggins PM|author-link=Philippa Wiggins|date=June 1996|title=High and low density water and resting, active and transformed cells|journal=Cell Biol. Int.|volume=20|issue=6|pages=429–35|doi=10.1006/cbir.1996.0054|pmid=8963257|s2cid=42866068}}</ref> 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.<ref>{{cite journal |vauthors=Persson E, Halle B |title=Cell water dynamics on multiple time scales |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=105 |issue=17 |pages=6266–71 |date=April 2008 |pmid=18436650 |pmc=2359779 |doi=10.1073/pnas.0709585105|bibcode=2008PNAS..105.6266P |doi-access=free }}</ref>

===Ions===
The concentrations of the other [[ion]]s 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.

{| class="wikitable" style="margin:auto; text-align:center;"
|+ Typical ion concentrations in mammalian cytosol and plasma.<ref name="Lodish-1999">{{cite book |author=Lodish, Harvey F. |title=Molecular cell biology |publisher=Scientific American Books |location=New York |year=1999 |isbn=0-7167-3136-3 |oclc=174431482 |url-access=registration |url=https://archive.org/details/molecularcellbio00lodi }}</ref>
|-
! rowspan=2 | Ion
! colspan=2 | [[Molar concentration|Concentration]] (millimolar)
|-
! In cytosol 
! In plasma
|-
| [[Potassium]]
| 139–150<ref>{{Cite journal|title=Potassium physiology|first=S. O.|last=Thier|date=April 25, 1986|journal=The American Journal of Medicine|volume=80|issue=4A|pages=3–7|doi=10.1016/0002-9343(86)90334-7|pmid=3706350}}</ref><ref name="Lote-2012">{{cite book |last=Lote |first=Christopher J. |title= Principles of Renal Physiology, 5th edition|page=12|year=2012|publisher=Springer}}</ref>
| 4
|-
| [[Sodium]]
| 12
| 145
|-
| [[Chloride]]
| 4
| 116
|-
| [[Bicarbonate]]
| 12
| 29
|-
| [[Amino acid]]s in proteins
| 138
| 9
|-
| [[Magnesium]]
| 0.8
| 1.5
|-
| [[Calcium]]
| <0.0002
| 1.8
|}

In contrast to extracellular fluid, cytosol has a high concentration of [[potassium]] ions and a low concentration of [[sodium]] ions.<ref name="Lang-2007">{{cite journal |author=Lang F |title=Mechanisms and significance of cell volume regulation |journal=J Am Coll Nutr |volume=26 |issue=5 Suppl |pages=613S–623S |date=October 2007 |pmid=17921474 |doi=10.1080/07315724.2007.10719667 |s2cid=1798009 }}</ref> 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]]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]]. 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.<ref name="Lang-2007"/>

Cells can deal with even larger osmotic changes by accumulating [[osmoprotectant]]s such as [[betaines]] or [[trehalose]] in their cytosol.<ref name="Lang-2007"/> 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]].<ref>{{cite journal |vauthors=Sussich F, Skopec C, Brady J, Cesàro A |title=Reversible dehydration of trehalose and anhydrobiosis: from solution state to an exotic crystal? |journal=Carbohydr. Res. |volume=334 |issue=3 |pages=165–76 |date=August 2001 |pmid=11513823 |doi=10.1016/S0008-6215(01)00189-6}}</ref> 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.<ref>{{cite journal |vauthors=Crowe JH, Carpenter JF, Crowe LM |title=The role of vitrification in anhydrobiosis |journal=[[Annu. Rev. Physiol.]] |volume=60 |pages=73–103 |year=1998 |pmid=9558455 |doi=10.1146/annurev.physiol.60.1.73}}</ref>

The low concentration of [[calcium]] in the cytosol allows calcium ions to function as a [[second messenger]] in [[calcium signaling]]. Here, a signal such as a [[hormone]] or an [[action potential]] opens [[calcium channel]] so that calcium floods into the cytosol.<ref>{{cite journal |author=Berridge MJ |title=Elementary and global aspects of calcium signalling |journal=J. Physiol. |volume=499 |issue= Pt 2|pages=291–306 |date=1 March 1997|pmid=9080360 |pmc=1159305 |doi=10.1113/jphysiol.1997.sp021927 |url=http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=9080360 }}</ref> This sudden increase in cytosolic calcium activates other signalling molecules, such as [[calmodulin]] and [[protein kinase C]].<ref>{{cite journal |vauthors=Kikkawa U, Kishimoto A, Nishizuka Y |title=The protein kinase C family: heterogeneity and its implications |journal=[[Annu. Rev. Biochem.]] |volume=58 |pages=31–44 |year=1989 |pmid=2549852 |doi=10.1146/annurev.bi.58.070189.000335}}</ref> Other ions such as chloride and potassium may also have signaling functions in the cytosol, but these are not well understood.<ref>{{cite journal |vauthors=Orlov SN, Hamet P |title=Intracellular monovalent ions as second messengers |journal=J. Membr. Biol. |volume=210 |issue=3 |pages=161–72 |date=April 2006 |pmid=16909338 |doi=10.1007/s00232-006-0857-9|s2cid=26068558 }}</ref>

===Macromolecules===
Protein molecules that do not bind to [[cell membrane]]s or the [[cytoskeleton]] are dissolved in the cytosol. The amount of protein in cells is extremely high, and approaches 200&nbsp;mg/ml, occupying about 20–30% of the volume of the cytosol.<ref name="Ellis-2001">{{cite journal |author=Ellis RJ |title=Macromolecular crowding: obvious but underappreciated |journal=Trends Biochem. Sci. |volume=26 |issue=10 |pages=597–604 |date=October 2001 |pmid=11590012 |doi=10.1016/S0968-0004(01)01938-7}}</ref> 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]].<ref name="James-1984"/> Indeed, in experiments where the plasma membrane of cells were carefully disrupted using [[saponin]], 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.<ref>{{cite journal |vauthors=Hudder A, Nathanson L, Deutscher MP |title=Organization of Mammalian Cytoplasm |journal=Mol. Cell. Biol. |volume=23 |issue=24 |pages=9318–26 |date=December 2003 |pmid=14645541 |pmc=309675 |doi=10.1128/MCB.23.24.9318-9326.2003}}</ref> However, the idea that the majority of the proteins in cells are tightly bound in a network called the [[microtrabecular lattice]] is now seen as unlikely.<ref>{{cite journal |author=Heuser J |title=Whatever happened to the 'microtrabecular concept'? |journal=Biol Cell |year=2002 |volume=94 |issue=9| pages=561–96  |doi=10.1016/S0248-4900(02)00013-8 |pmid=12732437|s2cid=45792524 }}</ref>

In prokaryotes the cytosol contains the cell's [[genome]], within a structure known as a [[nucleoid]].<ref>{{cite journal |vauthors=Thanbichler M, Wang S, Shapiro L |title=The bacterial nucleoid: a highly organized and dynamic structure |journal=J Cell Biochem |volume=96 |issue=3 |pages=506–21 |year=2005 |pmid=15988757 |doi=10.1002/jcb.20519|s2cid=25355087 |doi-access=free }}</ref> This is an irregular mass of [[DNA]] and associated proteins that control the [[transcription (genetics)|transcription]] and [[DNA replication|replication]] of the bacterial [[chromosome]] and [[plasmid]]s. In eukaryotes the genome is held within the [[cell nucleus]], which is separated from the cytosol by [[nuclear pore]]s that block the free diffusion of any molecule larger than about 10&nbsp;[[nanometre]]s in diameter.<ref>{{cite book |author=Peters R |chapter=Introduction to Nucleocytoplasmic Transport |title=Xenopus Protocols |volume=322 |pages=235–58 |year=2006 |pmid=16739728 |doi=10.1007/978-1-59745-000-3_17 |series=Methods in Molecular Biology |isbn=978-1-58829-362-6}}</ref>

This high concentration of macromolecules in cytosol causes an effect called [[macromolecular crowding]], which is when the [[activity (chemistry)|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 [[reaction rate|rates]] and the position of [[chemical equilibrium]] of reactions in the cytosol.<ref name="Ellis-2001"/> It is particularly important in its ability to alter [[dissociation constant]]s by favoring the association of macromolecules, such as when multiple proteins come together to form [[protein complex]]es, or when [[DNA-binding protein]]s bind to their targets in the [[genome]].<ref>{{cite journal |vauthors=Zhou HX, Rivas G, Minton AP |title=Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences |journal=[[Annu Rev Biophys]] |volume=37 |pages=375–97 |year=2008 |pmid=18573087 |doi=10.1146/annurev.biophys.37.032807.125817 |pmc=2826134}}</ref>

==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.<ref>{{cite journal |vauthors=Norris V, den Blaauwen T, Cabin-Flaman A |title=Functional Taxonomy of Bacterial Hyperstructures |journal=Microbiol. Mol. Biol. Rev. |volume=71 |issue=1 |pages=230–53 |date=March 2007 |pmid=17347523 |pmc=1847379 |doi=10.1128/MMBR.00035-06 }}</ref>

===Concentration gradients===
Although small molecules [[diffusion|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]].<ref>{{cite journal |vauthors=Wang SQ, Wei C, Zhao G |title=Imaging microdomain Ca2+ in muscle cells |journal=Circ. Res. |volume=94 |issue=8 |pages=1011–22 |date=April 2004 |pmid=15117829 |doi=10.1161/01.RES.0000125883.68447.A1 |doi-access=free }}</ref> These are about 2&nbsp;[[micrometre]]s in diameter and last for only a few [[millisecond]]s, although several sparks can merge to form larger gradients, called "calcium waves".<ref>{{cite journal |author=Jaffe LF |title=Classes and mechanisms of calcium waves |journal=[[Cell Calcium]] |volume=14 |issue=10 |pages=736–45 |date=November 1993 |pmid=8131190 |doi=10.1016/0143-4160(93)90099-R}}</ref> Concentration gradients of other small molecules, such as [[oxygen]] and [[adenosine triphosphate]] may be produced in cells around clusters of [[mitochondrion|mitochondria]], although these are less well understood.<ref>{{cite journal | author=Aw, T.Y. |year=2000 |title=Intracellular compartmentation of organelles and gradients of low molecular weight species |journal=Int Rev Cytol |volume=192 |pages=223–53 |doi=10.1016/S0074-7696(08)60528-8 |pmid=10553281 | series=International Review of Cytology | isbn=978-0-12-364596-8}}</ref><ref>{{cite journal |vauthors=Weiss JN, Korge P |title=The cytoplasm: no longer a well-mixed bag |journal=Circ. Res. |volume=89 |issue=2 |pages=108–10 |date=20 July 2001|pmid=11463714 |doi=10.1161/res.89.2.108 |doi-access=free }}</ref>

===Protein complexes===
Proteins can associate to form [[protein complex]]es, these often contain a set of proteins with similar functions, such as enzymes that carry out several steps in the same metabolic pathway.<ref>{{cite journal |author=Srere PA |title=Complexes of sequential metabolic enzymes |journal=[[Annu. Rev. Biochem.]] |volume=56 |pages=89–124 |year=1987 |pmid=2441660 |doi=10.1146/annurev.bi.56.070187.000513}}</ref> 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.<ref>{{cite journal |author=Perham RN |title=Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions |journal=[[Annu. Rev. Biochem.]] |volume=69 |pages=961–1004 |year=2000 |pmid=10966480 |doi=10.1146/annurev.biochem.69.1.961}}</ref> 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.<ref>{{cite journal |vauthors=Huang X, Holden HM, Raushel FM |s2cid=16722363 |title=Channeling of substrates and intermediates in enzyme-catalyzed reactions |journal=[[Annu. Rev. Biochem.]] |volume=70 |pages=149–80 |year=2001 |pmid=11395405 |doi=10.1146/annurev.biochem.70.1.149}}</ref> 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.<ref>{{cite journal |vauthors=Mowbray J, Moses V |title=The tentative identification in Escherichia coli of a multienzyme complex with glycolytic activity |journal=Eur. J. Biochem. |volume=66 |issue=1 |pages=25–36 |date=June 1976 |pmid=133800 |doi=10.1111/j.1432-1033.1976.tb10421.x}}</ref><ref>{{cite journal |vauthors=Srivastava DK, Bernhard SA |title=Metabolite transfer via enzyme-enzyme complexes |journal=Science |volume=234 |issue=4780 |pages=1081–6 |date=November 1986 |pmid=3775377 |doi=10.1126/science.3775377|bibcode=1986Sci...234.1081S }}</ref> Consequently, the importance of these complexes for metabolism in general remains unclear.

[[Image:Carboxysome.png|thumb|right|400px|[[Carboxysome]]s are protein-enclosed [[bacterial microcompartment]]s within the cytosol. On the left is an [[electron microscope]] image of carboxysomes, and on the right a model of their structure.]]

===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]].<ref>{{cite journal |vauthors=Groll M, Clausen T |title=Molecular shredders: how proteasomes fulfill their role |journal=Curr. Opin. Struct. Biol. |volume=13 |issue=6 |pages=665–73 |date=December 2003 |pmid=14675543 |doi=10.1016/j.sbi.2003.10.005}}</ref> Here, a set of subunits form a hollow barrel containing [[protease]]s 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.<ref>{{cite journal |vauthors=Nandi D, Tahiliani P, Kumar A, Chandu D |title=The ubiquitin-proteasome system |journal=J. Biosci. |volume=31 |issue=1 |pages=137–55 |date=March 2006 |pmid=16595883 |url=http://www.ias.ac.in/jbiosci/mar2006/137.pdf |archive-url=https://web.archive.org/web/20060702012628/http://www.ias.ac.in/jbiosci/mar2006/137.pdf |archive-date=2006-07-02 |url-status=live |doi=10.1007/BF02705243|s2cid=21603835 }}</ref>

Another large class of protein compartments are [[bacterial microcompartments]], which are made of a protein shell that encapsulates various enzymes.<ref name="Bobik-2007">{{cite journal|author=Bobik, T. A. |title=Bacterial Microcompartments |year=2007 |journal=Microbe |volume=2 |pages=25–31 |url=http://www.asm.org/ASM/files/ccLibraryFiles/Filename/000000002765/znw00107000025.pdf |publisher=Am Soc Microbiol |url-status=dead |archive-url=https://web.archive.org/web/20080802025916/http://www.asm.org/ASM/files/ccLibraryFiles/Filename/000000002765/znw00107000025.pdf |archive-date=2008-08-02 }}</ref> These compartments are typically about 100–200 [[nanometre]]s across and made of interlocking proteins.<ref>{{cite journal |vauthors=Yeates TO, Kerfeld CA, Heinhorst S, Cannon GC, Shively JM |title=Protein-based organelles in bacteria: carboxysomes and related microcompartments |journal=Nat. Rev. Microbiol. |volume=6 |pages=681–691 |date=August 2008 |pmid=18679172 |doi=10.1038/nrmicro1913 |issue=9|s2cid=22666203 }}</ref> A well-understood example is the [[carboxysome]], which contains enzymes involved in [[carbon fixation]] such as [[RuBisCO]].<ref>{{cite journal |vauthors=Badger MR, Price GD |title=CO<sub>2</sub> concentrating mechanisms in cyanobacteria: molecular components, their diversity and evolution |journal=J. Exp. Bot. |volume=54 |issue=383 |pages=609–22 |date=February 2003 |pmid=12554704 |doi=10.1093/jxb/erg076 |doi-access=free }}</ref>

===Biomolecular condensates===
Non-membrane bound organelles can form as [[biomolecular condensate]]s, which arise by clustering, [[oligomerisation]], or [[polymerisation]] of [[macromolecules]] to drive [[colloid]]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&nbsp;[[nanometre]]s (about the size of a [[ribosome]])<ref>{{cite journal |author=Cate JH |title=Construction of low-resolution x-ray crystallographic electron density maps of the ribosome |journal=Methods |volume=25 |issue=3 |pages=303–8 |date=November 2001 |pmid=11860284 |doi=10.1006/meth.2001.1242|url=https://zenodo.org/record/1229926 }}</ref>  were excluded from parts of the cytosol around the edges of the cell and next to the nucleus.<ref>{{cite journal |vauthors=Provance DW, McDowall A, Marko M, Luby-Phelps K |title=Cytoarchitecture of size-excluding compartments in living cells |journal=J. Cell Sci. |volume=106 |issue=2 |pages=565–77 |date=1 October 1993|doi=10.1242/jcs.106.2.565 |pmid=7980739 |url=http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=7980739 |url-access=subscription }}</ref><ref>{{cite journal |vauthors=Luby-Phelps K, Castle PE, Taylor DL, Lanni F |title=Hindered diffusion of inert tracer particles in the cytoplasm of mouse 3T3 cells |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=14 |pages=4910–3 |date=July 1987 |pmid=3474634 |pmc=305216 |doi=10.1073/pnas.84.14.4910|bibcode=1987PNAS...84.4910L |doi-access=free }}</ref> 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]]s and organelles within the cytosol by excluding them from some areas and concentrating them in others.<ref>{{cite journal |author=Luby-Phelps K |title=Effect of cytoarchitecture on the transport and localization of protein synthetic machinery |journal=J. Cell. Biochem. |volume=52 |issue=2 |pages=140–7 |date=June 1993 |pmid=8366131 |doi=10.1002/jcb.240520205|s2cid=12063324 }}</ref>

==Function==
The cytosol is the site of multiple cell processes. Examples of these processes include [[signal transduction]] from the cell membrane to sites within the cell, such as the [[cell nucleus]],<ref>{{cite journal |author=Kholodenko BN |title=Four-dimensional organization of protein kinase signaling cascades: the roles of diffusion, endocytosis and molecular motors |journal=J. Exp. Biol. |volume=206 |issue=Pt 12 |pages=2073–82 |date=June 2003 |pmid=12756289 |doi=10.1242/jeb.00298|s2cid=18002214 |doi-access= }}</ref> or organelles.<ref>{{cite journal |vauthors=Pesaresi P, Schneider A, Kleine T, Leister D |title=Interorganellar communication |journal=Curr. Opin. Plant Biol. |volume=10 |issue=6 |pages=600–6 |date=December 2007 |pmid=17719262 |doi=10.1016/j.pbi.2007.07.007}}</ref> This compartment is also the site of many of the processes of [[cytokinesis]], after the breakdown of the [[nuclear membrane]] in [[mitosis]].<ref>{{cite journal |vauthors=Winey M, Mamay CL, O'Toole ET |title=Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle |journal=J. Cell Biol. |volume=129 |issue=6 |pages=1601–15 |date=June 1995 |pmid=7790357 |pmc=2291174 |doi=10.1083/jcb.129.6.1601}}</ref> 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.<ref name="Verkman-2002"/> However, [[hydrophobe|hydrophobic]] molecules, such as [[fatty acid]]s or [[sterol]]s, can be transported through the cytosol by specific binding proteins, which shuttle these molecules between cell membranes.<ref>{{cite journal |author=Weisiger RA |title=Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands |journal=Mol. Cell. Biochem. |volume=239 |issue=1–2 |pages=35–43 |date=October 2002 |pmid=12479566 |doi=10.1023/A:1020550405578|s2cid=9608133 }}</ref><ref>{{cite journal |vauthors=Maxfield FR, Mondal M |title=Sterol and lipid trafficking in mammalian cells |journal=Biochem. Soc. Trans. |volume=34 |issue=Pt 3 |pages=335–9 |date=June 2006 |pmid=16709155 |doi=10.1042/BST0340335}}</ref> Molecules taken into the cell by [[endocytosis]] or on their way to be [[secretion|secreted]] can also be transported through the cytosol inside [[vesicle (biology)|vesicles]],<ref>{{cite journal |author=Pelham HR |title=The Croonian Lecture 1999. Intracellular membrane traffic: getting proteins sorted |journal=Philos. Trans. R. Soc. Lond. B Biol. Sci. |volume=354 |issue=1388 |pages=1471–8 |date=August 1999 |pmid=10515003 |pmc=1692657 |doi=10.1098/rstb.1999.0491 }}</ref> which are small spheres of lipids that are moved along the cytoskeleton by [[motor protein]]s.<ref>{{cite journal |vauthors=Kamal A, Goldstein LS |title=Principles of cargo attachment to cytoplasmic motor proteins |journal=Curr. Opin. Cell Biol. |volume=14 |issue=1 |pages=63–8 |date=February 2002 |pmid=11792546 |doi=10.1016/S0955-0674(01)00295-2}}</ref>

The cytosol is the site of most metabolism in prokaryotes,<ref name="Hoppert-1999">{{cite journal |vauthors=Hoppert M, Mayer F |title=Principles of macromolecular organization and cell function in bacteria and archaea |journal=Cell Biochem. Biophys. |volume=31 |issue=3 |pages=247–84 |year=1999 |pmid=10736750 |doi=10.1007/BF02738242|s2cid=21004307 }}</ref> 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.<ref>{{cite journal |vauthors=Foster LJ, de Hoog CL, Zhang Y |title=A mammalian organelle map by protein correlation profiling |journal=Cell |volume=125 |issue=1 |pages=187–99 |date=April 2006 |pmid=16615899 |doi=10.1016/j.cell.2006.03.022|s2cid=32197 |doi-access=free }}</ref> 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.<ref>{{cite journal |display-authors=9 |last1=Herrgård |first1=MJ |title=A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology |journal=Nature Biotechnology |volume=26 |issue=10 |pages=1155–60 |date=October 2008|doi=10.1038/nbt1492 |pmid=18846089 |last2=Swainston |first2=N |last3=Dobson |first3=P |last4=Dunn |first4=WB |last5=Arga |first5=KY |last6=Arvas |first6=M |last7=Blüthgen |first7=N |last8=Borger |first8=S |last9=Costenoble |first9=R |last10=Heinemann |first10=Matthias |last11=Hucka |first11=Michael |last12=Le Novère |first12=Nicolas |last13=Li |first13=Peter |last14=Liebermeister |first14=Wolfram |last15=Mo |first15=Monica L |last16=Oliveira |first16=Ana Paula |last17=Petranovic |first17=Dina |last18=Pettifer |first18=Stephen |last19=Simeonidis |first19=Evangelos |last20=Smallbone |first20=Kieran |last21=Spasić |first21=Irena |last22=Weichart |first22=Dieter |last23=Brent |first23=Roger |last24=Broomhead |first24=David S |last25=Westerhoff |first25=Hans V |last26=Kirdar |first26=Betül |last27=Penttilä |first27=Merja |last28=Klipp |first28=Edda |last29=Palsson |first29=Bernhard Ø |last30=Sauer |first30=Uwe |pmc=4018421}}</ref> Major metabolic pathways that occur in the cytosol in animals are [[protein biosynthesis]], the [[pentose phosphate pathway]], [[glycolysis]] and [[gluconeogenesis]].<ref>{{cite book |author1=Stryer, Lubert |author2=Berg, Jeremy Mark |author3=Tymoczko, John L. |title=Biochemistry |url=https://archive.org/details/biochemistry200100jere |url-access=registration |publisher=W.H. Freeman |location=San Francisco |year=2002 |isbn=0-7167-4684-0 |oclc=179705944}}</ref> The localization of pathways can be different in other organisms, for instance fatty acid synthesis occurs in [[chloroplast]]s in plants<ref>{{cite journal |vauthors=Ohlrogge J, Pollard M, Bao X |title=Fatty acid synthesis: from CO<sub>2</sub> to functional genomics |journal=Biochem. Soc. Trans. |volume=28 |issue=6 |pages=567–73 |date=December 2000 |pmid=11171129 |doi=10.1042/BST0280567}}</ref><ref>{{cite journal |vauthors=Ohlrogge JB, Kuhn DN, Stumpf PK |title=Subcellular localization of acyl carrier protein in leaf protoplasts of Spinacia oleracea |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=76 |issue=3 |pages=1194–8 |date=March 1979 |pmid=286305 |pmc=383216 |doi=10.1073/pnas.76.3.1194|bibcode=1979PNAS...76.1194O |doi-access=free }}</ref> and in [[apicoplast]]s in [[apicomplexa]].<ref>{{cite journal |vauthors=Goodman CD, McFadden GI |s2cid=2565225 |title=Fatty acid biosynthesis as a drug target in apicomplexan parasites |journal=Curr Drug Targets |volume=8 |issue=1 |pages=15–30 |date=January 2007 |pmid=17266528 |doi=10.2174/138945007779315579}}</ref>

==References==
{{Reflist|30em}}

==Further reading==
*{{cite book |author1=Wheatley, Denys N. |author2=Pollack, Gerald H. |author3=Cameron, Ivan L. |title=Water and the Cell |publisher=Springer |location=Berlin |year=2006 |isbn=1-4020-4926-9 |oclc=71298997}}

{{Cellular structures}}
{{Authority control}}
{{Good article}}

[[Category:Cell anatomy]]
[[Category:Cytoplasm]]