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Mitochondrial matrix

In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.[1]

Cell biology
mitochondrion
Components of a typical mitochondrion

1 Outer membrane

1.1 Porin

2 Intermembrane space

2.1 Intracristal space
2.2 Peripheral space

3 Lamella

3.1 Inner membrane
3.11 Inner boundary membrane
3.12 Cristal membrane
3.2 Matrix   ◄ You are here
3.3 Cristæ

4 Mitochondrial DNA
5 Matrix granule
6 Ribosome
7 ATP synthase


The composition of the matrix based on its structures and contents produce an environment that allows the anabolic and catabolic pathways to proceed favorably. The electron transport chain and enzymes in the matrix play a large role in the citric acid cycle and oxidative phosphorylation. The citric acid cycle produces NADH and FADH2 through oxidation that will be reduced in oxidative phosphorylation to produce ATP.[2][3]

The cytosolic, intermembrane space, compartment has a higher aqueous:protein content of around 3.8 μL/mg protein relative to that occurring in mitochondrial matrix where such levels typically are near 0.8 μL/mg protein.[4] It is not known how mitochondria maintain osmotic balance across the inner mitochondrial membrane, although the membrane contains aquaporins that are believed to be conduits for regulated water transport. Mitochondrial matrix has a pH of about 7.8, which is higher than the pH of the intermembrane space of the mitochondria, which is around 7.0–7.4.[5] Mitochondrial DNA was discovered by Nash and Margit in 1963. One to many double stranded mainly circular DNA is present in mitochondrial matrix. Mitochondrial DNA is 1% of total DNA of a cell. It is rich in guanine and cytosine content, and in humans is maternally derived. Mitochondria of mammals have 55s ribosomes.

Composition

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Metabolites

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The matrix is host to a wide variety of metabolites involved in processes within the matrix. The citric acid cycle involves acyl-CoA, pyruvate, acetyl-CoA, citrate, isocitrate, α-ketoglutarate, succinyl-CoA, fumarate, succinate, L-malate, and oxaloacetate.[2] The urea cycle makes use of L-ornithine, carbamoyl phosphate, and L-citrulline.[4] The electron transport chain oxidizes coenzymes NADH and FADH2. Protein synthesis makes use of mitochondrial DNA, RNA, and tRNA.[5] Regulation of processes makes use of ions (Ca2+/K+/Mg+).[6] Additional metabolites present in the matrix are CO2, H2O, O2, ATP, ADP, and Pi.[1]

Enzymes

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Enzymes from processes that take place in the matrix. The citric acid cycle is facilitated by pyruvate dehydrogenase, citrate synthase, aconitase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinyl-CoA synthetase, fumarase, and malate dehydrogenase.[2] The urea cycle is facilitated by carbamoyl phosphate synthetase I and ornithine transcarbamylase.[4] β-Oxidation uses pyruvate carboxylase, acyl-CoA dehydrogenase, and β-ketothiolase.[1] Amino acid production is facilitated by transaminases.[7] Amino acid metabolism is mediated by proteases, such as presequence protease.[8]

Inner membrane components

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The inner membrane is a phospholipid bilayer that contains the complexes of oxidative phosphorylation. which contains the electron transport chain that is found on the cristae of the inner membrane and consists of four protein complexes and ATP synthase. These complexes are complex I (NADH:coenzyme Q oxidoreductase), complex II (succinate:coenzyme Q oxidoreductase), complex III (coenzyme Q: cytochrome c oxidoreductase), and complex IV (cytochrome c oxidase).[6]

Inner membrane control over matrix composition

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The electron transport chain is responsible for establishing a pH and electrochemical gradient that facilitates the production of ATP through the pumping of protons. The gradient also provides control of the concentration of ions such as Ca2+ driven by the mitochondrial membrane potential.[1] The membrane only allows nonpolar molecules such as CO2 and O2 and small non charged polar molecules such as H2O to enter the matrix. Molecules enter and exit the mitochondrial matrix through transport proteins and ion transporters. Molecules are then able to leave the mitochondria through porin.[9] These attributed characteristics allow for control over concentrations of ions and metabolites necessary for regulation and determines the rate of ATP production.[10][11]

Processes

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Citric acid cycle

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Following glycolysis, the citric acid cycle is activated by the production of acetyl-CoA. The oxidation of pyruvate by pyruvate dehydrogenase in the matrix produces CO2, acetyl-CoA, and NADH. Beta oxidation of fatty acids serves as an alternate catabolic pathway that produces acetyl-CoA, NADH, and FADH2.[1] The production of acetyl-CoA begins the citric acid cycle while the co-enzymes produced are used in the electron transport chain.[11]

 
ATP synthesis as seen from the perspective of the matrix. Conditions produced by the relationships between the catabolic pathways (citric acid cycle and oxidative phosphorylation) and structural makeup (lipid bilayer and electron transport chain) of matrix facilitate ATP synthesis.

All of the enzymes for the citric acid cycle are in the matrix (e.g. citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, fumarase, and malate dehydrogenase) except for succinate dehydrogenase which is on the inner membrane and is part of protein complex II in the electron transport chain. The cycle produces coenzymes NADH and FADH2 through the oxidation of carbons in two cycles. The oxidation of NADH and FADH2 produces GTP from succinyl-CoA synthetase.[2]

Oxidative phosphorylation

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NADH and FADH2 are produced in the matrix or transported in through porin and transport proteins in order to undergo oxidation through oxidative phosphorylation.[1] NADH and FADH2 undergo oxidation in the electron transport chain by transferring an electrons to regenerate NAD+ and FAD. Protons are pulled into the intermembrane space by the energy of the electrons going through the electron transport chain. Four electrons are finally accepted by oxygen in the matrix to complete the electron transport chain. The protons return to the mitochondrial matrix through the protein ATP synthase. The energy is used in order to rotate ATP synthase which facilitates the passage of a proton, producing ATP. A pH difference between the matrix and intermembrane space creates an electrochemical gradient by which ATP synthase can pass a proton into the matrix favorably.[6]

Urea cycle

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The first two steps of the urea cycle take place within the mitochondrial matrix of liver and kidney cells. In the first step ammonia is converted into carbamoyl phosphate through the investment of two ATP molecules. This step is facilitated by carbamoyl phosphate synthetase I. The second step facilitated by ornithine transcarbamylase converts carbamoyl phosphate and ornithine into citrulline. After these initial steps the urea cycle continues in the inner membrane space until ornithine once again enters the matrix through a transport channel to continue the first to steps within matrix.[12]

Transamination

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α-Ketoglutarate and oxaloacetate can be converted into amino acids within the matrix through the process of transamination. These reactions are facilitated by transaminases in order to produce aspartate and asparagine from oxaloacetate. Transamination of α-ketoglutarate produces glutamate, proline, and arginine. These amino acids are then used either within the matrix or transported into the cytosol to produce proteins.[7][13]

Regulation

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Regulation within the matrix is primarily controlled by ion concentration, metabolite concentration and energy charge. Availability of ions such as Ca2+ control various functions of the citric acid cycle. in the matrix activates pyruvate dehydrogenase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase which increases the reaction rate in the cycle.[14] Concentration of intermediates and coenzymes in the matrix also increase or decrease the rate of ATP production due to anaplerotic and cataplerotic effects. NADH can act as an inhibitor for α-ketoglutarate, isocitrate dehydrogenase, citrate synthase, and pyruvate dehydrogenase. The concentration of oxaloacetate in particular is kept low, so any fluctuations in this concentrations serve to drive the citric acid cycle forward.[2] The production of ATP also serves as a means of regulation by acting as an inhibitor for isocitrate dehydrogenase, pyruvate dehydrogenase, the electron transport chain protein complexes, and ATP synthase. ADP acts as an activator.[1]

Protein synthesis

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The mitochondria contains its own set of DNA used to produce proteins found in the electron transport chain. The mitochondrial DNA only codes for about thirteen proteins that are used in processing mitochondrial transcripts, ribosomal proteins, ribosomal RNA, transfer RNA, and protein subunits found in the protein complexes of the electron transport chain.[15][16]

See also

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References

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  1. ^ a b c d e f g Voet, Donald; Voet, Judith; Pratt, Charlotte (2013). Fundamentals of Biochemistry Life at the Molecular Level. New York City: John Wiley & Sons, Inc. pp. 582–584. ISBN 978-1118129180.
  2. ^ a b c d e Stryer, L; Berg, J; Tymoczko, JL (2002). Biochemistry. San Francisco: W.H. Freeman. pp. 509–527, 569–579, 614–616, 638–641, 732–735, 739–748, 770–773. ISBN 978-0-7167-4684-3.
  3. ^ Mitchell, Peter; Moyle, Jennifer (1967-01-14). "Chemiosmotic Hypothesis of Oxidative Phosphorylation". Nature. 213 (5072): 137–139. Bibcode:1967Natur.213..137M. doi:10.1038/213137a0. PMID 4291593. S2CID 4149605.
  4. ^ a b c Soboll, S; Scholz, R; Freisl, M; Elbers, R; Heldt, H.W. (1976). Distribution of metabolites between mitochondria and cytosol of perfused liver. New york: Elsevier. pp. 29–40. ISBN 978-0-444-10925-5.
  5. ^ a b Porcelli, Anna Maria; Ghelli, Anna; Zanna, Claudia; Pinton, Paolo; Rizzuto, Rosario; Rugolo, Michela (2005-01-28). "pH difference across the outer mitochondrial membrane measured with a green fluorescent protein mutant". Biochemical and Biophysical Research Communications. 326 (4): 799–804. doi:10.1016/j.bbrc.2004.11.105. PMID 15607740.
  6. ^ a b c Dimroth, P.; Kaim, G.; Matthey, U. (2000-01-01). "Crucial role of the membrane potential for ATP synthesis by F(1)F(o) ATP synthases". The Journal of Experimental Biology. 203 (Pt 1): 51–59. doi:10.1242/jeb.203.1.51. ISSN 0022-0949. PMID 10600673.
  7. ^ a b Karmen, A.; Wroblewski, F.; Ladue, J. S. (1955-01-01). "Transaminase activity in human blood". The Journal of Clinical Investigation. 34 (1): 126–131. doi:10.1172/JCI103055. ISSN 0021-9738. PMC 438594. PMID 13221663.
  8. ^ King, John V.; Liang, Wenguang G.; Scherpelz, Kathryn P.; Schilling, Alexander B.; Meredith, Stephen C.; Tang, Wei-Jen (2014-07-08). "Molecular basis of substrate recognition and degradation by human presequence protease". Structure. 22 (7): 996–1007. doi:10.1016/j.str.2014.05.003. ISSN 1878-4186. PMC 4128088. PMID 24931469.
  9. ^ Alberts, Bruce; Johnson, Alexander; Lewis, julian; Roberts, Keith; Peters, Walter; Raff, Martin (1994). Molecular Biology of the Cell. New york: Garland Publishing Inc. ISBN 978-0-8153-3218-3.
  10. ^ Anderson, S.; Bankier, A. T.; Barrell, B. G.; de Bruijn, M. H. L.; Coulson, A. R.; Drouin, J.; Eperon, I. C.; Nierlich, D. P.; Roe, B. A. (1981-04-09). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–465. Bibcode:1981Natur.290..457A. doi:10.1038/290457a0. PMID 7219534. S2CID 4355527.
  11. ^ a b Iuchi, S.; Lin, E. C. C. (1993-07-01). "Adaptation of Escherichia coli to redox environments by gene expression". Molecular Microbiology. 9 (1): 9–15. doi:10.1111/j.1365-2958.1993.tb01664.x. ISSN 1365-2958. PMID 8412675. S2CID 39165641.
  12. ^ Tuchman, Mendel; Plante, Robert J. (1995-01-01). "Mutations and polymorphisms in the human ornithine transcarbamylase gene: Mutation update addendum". Human Mutation. 5 (4): 293–295. doi:10.1002/humu.1380050404. ISSN 1098-1004. PMID 7627182. S2CID 2951786.
  13. ^ Kirsch, Jack F.; Eichele, Gregor; Ford, Geoffrey C.; Vincent, Michael G.; Jansonius, Johan N.; Gehring, Heinz; Christen, Philipp (1984-04-15). "Mechanism of action of aspartate aminotransferase proposed on the basis of its spatial structure". Journal of Molecular Biology. 174 (3): 497–525. doi:10.1016/0022-2836(84)90333-4. PMID 6143829.
  14. ^ Denton, Richard M.; Randle, Philip J.; Bridges, Barbara J.; Cooper, Ronald H.; Kerbey, Alan L.; Pask, Helen T.; Severson, David L.; Stansbie, David; Whitehouse, Susan (1975-10-01). "Regulation of mammalian pyruvate dehydrogenase". Molecular and Cellular Biochemistry. 9 (1): 27–53. doi:10.1007/BF01731731. ISSN 0300-8177. PMID 171557. S2CID 27367543.
  15. ^ Fox, Thomas D. (2012-12-01). "Mitochondrial Protein Synthesis, Import, and Assembly". Genetics. 192 (4): 1203–1234. doi:10.1534/genetics.112.141267. ISSN 0016-6731. PMC 3512135. PMID 23212899.
  16. ^ Grivell, L.A.; Pel, H.J. (1994). "Protein synthesis in mitochondria" (PDF). Mol. Biol. Rep. 19 (3): 183–194. doi:10.1007/bf00986960. PMID 7969106. S2CID 21200502.
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