Cytosol

Cytosol

The cytosol is a crowded solution of many different types of molecules that fills much of the volume of cells.[1]
Cell biology
The animal cell
Components of a typical animal cell:
  1. Nucleolus
  2. Nucleus
  3. Ribosome (little dots)
  4. Vesicle
  5. Rough endoplasmic reticulum
  6. Golgi apparatus (or "Golgi body")
  7. Cytoskeleton
  8. Smooth endoplasmic reticulum
  9. Mitochondrion
  10. Vacuole
  11. Cytosol (fluid that contains organelles)
  12. Lysosome
  13. Centrosome
  14. Cell membrane

The cytosol or intracellular fluid (ICF) or cytoplasmic matrix is the liquid found inside cells. It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments.

In the cell nucleus is separate. 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 pathways still occur in the cytosol, others are contained 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 are different in the cytosol than in the extracellular fluid; these differences in ion levels are important in processes such as osmoregulation and cell signaling. The cytosol also contains large amounts of macromolecules, 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 gradients of small molecules such as calcium, large complexes of enzymes that act together to carry out metabolic pathways, and protein complexes such as proteasomes and carboxysomes that enclose and separate parts of the cytosol.

Contents

  • Definition 1
  • Properties and composition 2
    • Water 2.1
    • Ions 2.2
    • Macromolecules 2.3
  • Organization 3
    • Concentration gradients 3.1
    • Protein complexes 3.2
    • Protein compartments 3.3
    • Cytoskeletal sieving 3.4
  • Function 4
  • References 5
  • Further reading 6

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

  • Wheatley, Denys N.; Pollack, Gerald H.; Cameron, Ivan L. (2006). Water and the Cell. Berlin: Springer.  

Further reading

  1. ^ Goodsell DS (June 1991). "Inside a living cell". Trends Biochem. Sci. 16 (6): 203–6.  
  2. ^ a b c d e Clegg JS (February 1984). "Properties and metabolism of the aqueous cytoplasm and its boundaries". Am. J. Physiol. 246 (2 Pt 2): R133–51.  
  3. ^ a b Cammack, Richard; Teresa Atwood; Attwood, Teresa K.; Campbell, Peter Scott; Parish, Howard I.; Smith, Tony; Vella, Frank; Stirling, John (2006). Oxford dictionary of biochemistry and molecular biology. Oxford [Oxfordshire]: Oxford University Press.  
  4. ^ a b Lodish, Harvey F. (1999). Molecular cell biology. New York: Scientific American Books.  
  5. ^ a b
  6. ^ Bowsher CG, Tobin AK (April 2001). "Compartmentation of metabolism within mitochondria and plastids". J. Exp. Bot. 52 (356): 513–27.  
  7. ^ Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB (May 2004). "Metabolomics by numbers: acquiring and understanding global metabolite data" (PDF). Trends Biotechnol. 22 (5): 245–52.  
  8. ^ Weckwerth W (2003). "Metabolomics in systems biology". Annu Rev Plant Biol 54: 669–89.  
  9. ^ Reed JL, Vo TD, Schilling CH, Palsson BO (2003). "An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR)". Genome Biol. 4 (9): R54.  
  10. ^ Förster J, Famili I, Fu P, Palsson BØ, Nielsen J (February 2003). "Genome-Scale Reconstruction of the Saccharomyces cerevisiae Metabolic Network". Genome Res. 13 (2): 244–53.  
  11. ^ Luby-Phelps K (2000). "Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area". Int. Rev. Cytol. International Review of Cytology 192: 189–221.  
  12. ^ Roos A, Boron WF (April 1981). "Intracellular pH". Physiol. Rev. 61 (2): 296–434.  
  13. ^ Bright, G R; Fisher, GW; Rogowska, J; Taylor, DL (1987). "Fluorescence ratio imaging microscopy: temporal and spatial measurements of cytoplasmic pH". The Journal of Cell Biology 104 (4): 1019–1033.  
  14. ^ a b Verkman AS (January 2002). "Solute and macromolecule diffusion in cellular aqueous compartments". Trends Biochem. Sci. 27 (1): 27–33.  
  15. ^ a b Wiggins PM (1 December 1990). "Role of water in some biological processes". Microbiol. Rev. 54 (4): 432–49.  
  16. ^ Fulton AB (September 1982). "How crowded is the cytoplasm?". Cell 30 (2): 345–7.  
  17. ^ Garlid KD (2000). "The state of water in biological systems". Int. Rev. Cytol. International Review of Cytology 192: 281–302.  
  18. ^ Chaplin M (November 2006). "Do we underestimate the importance of water in cell biology?". Nat. Rev. Mol. Cell Biol. 7 (11): 861–6.  
  19. ^ Wiggins PM (June 1996). "High and low density water and resting, active and transformed cells". Cell Biol. Int. 20 (6): 429–35.  
  20. ^ Persson E, Halle B (April 2008). "Cell water dynamics on multiple time scales". Proc. Natl. Acad. Sci. U.S.A. 105 (17): 6266–71.  
  21. ^ a b c Lang F (October 2007). "Mechanisms and significance of cell volume regulation". J Am Coll Nutr 26 (5 Suppl): 613S–623S.  
  22. ^ Sussich F, Skopec C, Brady J, Cesàro A (August 2001). "Reversible dehydration of trehalose and anhydrobiosis: from solution state to an exotic crystal?". Carbohydr. Res. 334 (3): 165–76.  
  23. ^ Crowe JH, Carpenter JF, Crowe LM (1998). "The role of vitrification in anhydrobiosis". Annu. Rev. Physiol. 60: 73–103.  
  24. ^ Berridge MJ (1 March 1997). "Elementary and global aspects of calcium signalling". J. Physiol. (Lond.) 499 (Pt 2): 291–306.  
  25. ^ Kikkawa U, Kishimoto A, Nishizuka Y (1989). "The protein kinase C family: heterogeneity and its implications". Annu. Rev. Biochem. 58: 31–44.  
  26. ^ Orlov SN, Hamet P (April 2006). "Intracellular monovalent ions as second messengers". J. Membr. Biol. 210 (3): 161–72.  
  27. ^ a b Ellis RJ (October 2001). "Macromolecular crowding: obvious but underappreciated". Trends Biochem. Sci. 26 (10): 597–604.  
  28. ^ Hudder A, Nathanson L, Deutscher MP (December 2003). "Organization of Mammalian Cytoplasm". Mol. Cell. Biol. 23 (24): 9318–26.  
  29. ^ Heuser J (2002). "Whatever happened to the 'microtrabecular concept'?". Biol Cell 94 (9): 561–96.  
  30. ^ Thanbichler M, Wang S, Shapiro L (2005). "The bacterial nucleoid: a highly organized and dynamic structure". J Cell Biochem 96 (3): 506–21.  
  31. ^ Peters R (2006). "Introduction to nucleocytoplasmic transport: molecules and mechanisms". Methods Mol. Biol. Methods in Molecular Biology™ 322: 235–58.  
  32. ^ Zhou HX, Rivas G, Minton AP (2008). "Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences". Annu Rev Biophys 37: 375–97.  
  33. ^ Norris V, den Blaauwen T, Cabin-Flaman A (March 2007). "Functional Taxonomy of Bacterial Hyperstructures". Microbiol. Mol. Biol. Rev. 71 (1): 230–53.  
  34. ^ Wang SQ, Wei C, Zhao G (April 2004). "Imaging microdomain Ca2+ in muscle cells". Circ. Res. 94 (8): 1011–22.  
  35. ^ Jaffe LF (November 1993). "Classes and mechanisms of calcium waves".  
  36. ^ Aw, T.Y. (2000). "Intracellular compartmentation of organelles and gradients of low molecular weight species". Int Rev Cytol. International Review of Cytology 192: 223–53.  
  37. ^ Weiss JN, Korge P (20 July 2001). "The cytoplasm: no longer a well-mixed bag". Circ. Res. 89 (2): 108–10.  
  38. ^ Srere PA (1987). "Complexes of sequential metabolic enzymes". Annu. Rev. Biochem. 56: 89–124.  
  39. ^ Perham RN (2000). "Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions". Annu. Rev. Biochem. 69: 961–1004.  
  40. ^ Huang X, Holden HM, Raushel FM (2001). "Channeling of substrates and intermediates in enzyme-catalyzed reactions". Annu. Rev. Biochem. 70: 149–80.  
  41. ^ Mowbray J, Moses V (June 1976). "The tentative identification in Escherichia coli of a multienzyme complex with glycolytic activity". Eur. J. Biochem. 66 (1): 25–36.  
  42. ^ Srivastava DK, Bernhard SA (November 1986). "Metabolite transfer via enzyme-enzyme complexes". Science 234 (4780): 1081–6.  
  43. ^ Groll M, Clausen T (December 2003). "Molecular shredders: how proteasomes fulfill their role". Curr. Opin. Struct. Biol. 13 (6): 665–73.  
  44. ^ Nandi D, Tahiliani P, Kumar A, Chandu D (March 2006). "The ubiquitin-proteasome system" (PDF). J. Biosci. 31 (1): 137–55.  
  45. ^ Bobik, T. A. (2007). "Bacterial Microcompartments" (PDF). Microbe (Am Soc Microbiol) 2: 25–31. 
  46. ^ Yeates TO, Kerfeld CA, Heinhorst S, Cannon GC, Shively JM (August 2008). "Protein-based organelles in bacteria: carboxysomes and related microcompartments". Nat. Rev. Microbiol. 6 (9): 681–691.  
  47. ^ Badger MR, Price GD (February 2003). concentrating mechanisms in cyanobacteria: molecular components, their diversity and evolution"2"CO. J. Exp. Bot. 54 (383): 609–22.  
  48. ^ Cate JH (November 2001). "Construction of low-resolution x-ray crystallographic electron density maps of the ribosome". Methods 25 (3): 303–8.  
  49. ^ Provance DW, McDowall A, Marko M, Luby-Phelps K (1 October 1993). "Cytoarchitecture of size-excluding compartments in living cells". J. Cell. Sci. 106 (2): 565–77.  
  50. ^ Luby-Phelps K, Castle PE, Taylor DL, Lanni F (July 1987). "Hindered diffusion of inert tracer particles in the cytoplasm of mouse 3T3 cells". Proc. Natl. Acad. Sci. U.S.A. 84 (14): 4910–3.  
  51. ^ Luby-Phelps K (June 1993). "Effect of cytoarchitecture on the transport and localization of protein synthetic machinery". J. Cell. Biochem. 52 (2): 140–7.  
  52. ^ Kholodenko BN (June 2003). "Four-dimensional organization of protein kinase signaling cascades: the roles of diffusion, endocytosis and molecular motors". J. Exp. Biol. 206 (Pt 12): 2073–82.  
  53. ^ Pesaresi P, Schneider A, Kleine T, Leister D (December 2007). "Interorganellar communication". Curr. Opin. Plant Biol. 10 (6): 600–6.  
  54. ^ Winey M, Mamay CL, O'Toole ET (June 1995). "Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle". J. Cell Biol. 129 (6): 1601–15.  
  55. ^ Weisiger RA (October 2002). "Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands". Mol. Cell. Biochem. 239 (1–2): 35–43.  
  56. ^ Maxfield FR, Mondal M (June 2006). "Sterol and lipid trafficking in mammalian cells". Biochem. Soc. Trans. 34 (Pt 3): 335–9.  
  57. ^ Pelham HR (August 1999). "The Croonian Lecture 1999. Intracellular membrane traffic: getting proteins sorted". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 354 (1388): 1471–8.  
  58. ^ Kamal A, Goldstein LS (February 2002). "Principles of cargo attachment to cytoplasmic motor proteins". Curr. Opin. Cell Biol. 14 (1): 63–8.  
  59. ^ Foster LJ, de Hoog CL, Zhang Y (April 2006). "A mammalian organelle map by protein correlation profiling". Cell 125 (1): 187–99.  
  60. ^
  61. ^ Stryer, Lubert; Berg, Jeremy Mark; Tymoczko, John L. (2002). Biochemistry. San Francisco: W.H. Freeman.  
  62. ^
  63. ^ Ohlrogge JB, Kuhn DN, Stumpf PK (March 1979). "Subcellular localization of acyl carrier protein in leaf protoplasts of Spinacia oleracea". Proc. Natl. Acad. Sci. U.S.A. 76 (3): 1194–8.  
  64. ^ Goodman CD, McFadden GI (January 2007). "Fatty acid biosynthesis as a drug target in apicomplexan parasites". Curr Drug Targets 8 (1): 15–30.  

References

The cytosol is the site of most metabolism in prokaryotes,[5] 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.[59] 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.[60] Major metabolic pathways that occur in the cytosol in animals are chloroplasts in plants[62][63] and in apicoplasts in apicomplexa.[64]

[58].motor proteins which are small spheres of lipids that are moved along the cytoskeleton by [57],vesicles can also be transported through the cytosol inside secreted or on their way to be endocytosis Molecules taken into the cell by [56][55], can be transported through the cytosol by specific binding proteins, which shuttle these molecules between cell membranes.sterols or fatty acids molecules, such as hydrophobic However, [14] 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.[54].mitosis in nuclear membrane, after the breakdown of the cytokinesis This compartment is also the site of many of the processes of [53] The cytosol has no single function and is instead the site of multiple cell processes. Examples of these processes include

Function

[51] Although the

Cytoskeletal sieving

Another large class of protein compartments are bacterial microcompartments, which are made of a protein shell that encapsulates various enzymes.[45] These compartments are typically about 100-200 nanometres across and made of interlocking proteins.[46] A well-understood example is the carboxysome, which contains enzymes involved in carbon fixation such as RuBisCO.[47]

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.[43] 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.[44]

Protein compartments

Carboxysomes are protein-enclosed bacterial microcompartments within the cytosol. On the left is an electron microscope image of carboxysomes, and on the right a model of their structure.

Proteins can associate to form 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.[39] 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.[40] 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.[41][42] Consequently, the importance of these complexes for metabolism in general remains unclear.

Protein complexes

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.[34] These are about 2 micrometres in diameter and last for only a few milliseconds, although several sparks can merge to form larger gradients, called "calcium waves".[35] Concentration gradients of other small molecules, such as oxygen and adenosine triphosphate may be produced in cells around clusters of mitochondria, although these are less well understood.[36][37]

Concentration gradients

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.[33]

Organization

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 and the position of chemical equilibrium of reactions in the cytosol.[27] It is particularly important in its ability to alter dissociation constants 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.[32]

In prokaryotes the cytosol contains the cell's genome, within a structure known as a nucleoid.[30] This is an irregular mass of DNA and associated proteins that control the transcription and replication of the bacterial chromosome and plasmids. In eukaryotes the genome is held within the cell nucleus, which is separated from the cytosol by nuclear pores that block the free diffusion of any molecule larger than about 10 nanometres in diameter.[31]

[29] is now seen as unlikely.microtrabecular lattice However, the idea that the majority of the proteins in cells are tightly bound in a network called the [28], 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.saponin Indeed, in experiments where the plasma membrane of cells were carefully disrupted using [2] Protein molecules that do not bind to

Macromolecules

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 channels so that calcium floods into the cytosol.[24] This sudden increase in cytosolic calcium activates other signalling molecules, such as calmodulin and protein kinase C.[25] Other ions such as chloride and potassium may also have signaling functions in the cytosol, but these are not well understood.[26]

Cells can deal with even larger osmotic changes by accumulating cryptobiosis.[22] 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.[23]

[21] In contrast to extracellular fluid, cytosol has a high concentration of

Typical ion concentrations in mammalian cytosol and blood.[4]
Ion  Concentration in cytosol (millimolar  Concentration in blood (millimolar
 Potassium   139   4 
 Sodium   12   145 
 Chloride   4   116 
 Bicarbonate   12   29 
 Amino acids in proteins   138   9 
 Magnesium   0.8   1.5 
 Calcium   <0.0002   1.8 

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.

Ions

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.[2] 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.[16][17] 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.[18] 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.[15][19] 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.[20]

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 clusters through hydrogen bonds.[15]

Most of the cytosol is water, which makes up about 70% of the total volume of a typical cell.[11] The pH of the intracellular fluid is 7.4.[12] while human cytosolic pH ranges between 7.0 - 7.4, and is usually higher if a cell is growing.[13] 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 macromolecules in the cytosol.[14] 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.[2]

Water

The proportion of cell volume that is cytosol varies: for example while this compartment forms the bulk of cell structure in bacteria,[5] in plant cells the main compartment is the large central vacuole.[6] 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.[7] This mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism (the metabolites) 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.[8] Estimates of the number of metabolites in single cells such as E. coli and baker's yeast predict that under 1,000 are made.[9][10]

Intracellular fluid content in humans

Properties and composition

[2] 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.[4]