Editing Mitochondrial matrix

{{short description|Space within the inner membrane of the mitochondrion}}
{{Cell biology|mitochondrion=yes}}
In the [[mitochondrion]], the '''matrix''' is the space within the [[Inner mitochondrial membrane|inner membrane]]. It can also be referred as the mitochondrial fluid. 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]], [[ribosome]]s, soluble [[enzyme]]s, small organic molecules, [[nucleotide]] cofactors, and [[inorganic ions]].<sup>[1]</sup> The enzymes in the matrix facilitate reactions responsible for the production of [[Adenosine triphosphate|ATP]], such as the [[citric acid cycle]], [[oxidative phosphorylation]], oxidation of [[pyruvate]], and the [[Beta oxidation|beta oxidation of fatty acids]].<ref name=":0">{{Cite book|title=Fundamentals of Biochemistry Life at the Molecular Level|last1=Voet|first1=Donald|last2=Voet|first2=Judith|last3=Pratt|first3=Charlotte|publisher=John Wiley & Sons, Inc.|year=2013|isbn=978-1118129180|location=New York City|pages=582–584}}</ref>

The composition of the matrix based on its structures and contents produce an environment that allows the [[Anabolism|anabolic]] and [[Catabolism|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 [[Nicotinamide adenine dinucleotide|NADH]] and [[Flavin adenine dinucleotide|FADH2]] through oxidation that will be reduced in [[oxidative phosphorylation]] to produce [[Adenosine triphosphate|ATP]].<ref name=":1">{{Cite book|title=Biochemistry|last1=Stryer|first1=L|last2=Berg|first2=J|last3=Tymoczko|first3=JL|publisher=W.H. Freeman|year=2002|isbn=978-0-7167-4684-3|location=San Francisco|pages=509–527, 569–579, 614–616, 638–641, 732–735, 739–748, 770–773}}</ref><ref>{{Cite journal|last1=Mitchell|first1=Peter|last2=Moyle|first2=Jennifer|date=1967-01-14|title=Chemiosmotic Hypothesis of Oxidative Phosphorylation|journal=Nature|language=en|volume=213|issue=5072|pages=137–139|doi=10.1038/213137a0|pmid=4291593|bibcode=1967Natur.213..137M |s2cid=4149605 }}</ref>

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.<ref name=":5">{{Cite book|title=Distribution of metabolites between mitochondria and cytosol of perfused liver|last1=Soboll|first1=S|last2=Scholz|first2=R|last3=Freisl|first3=M|last4=Elbers|first4=R|last5=Heldt|first5=H.W.|publisher=Elsevier|year=1976|isbn=978-0-444-10925-5|location=New york|pages=29–40}}</ref> It is not known how mitochondria maintain [[Osmosis|osmotic]] balance across the inner mitochondrial membrane, although the membrane contains [[aquaporin]]s 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.<ref name=":6">{{Cite journal|last1=Porcelli|first1=Anna Maria|last2=Ghelli|first2=Anna|last3=Zanna|first3=Claudia|last4=Pinton|first4=Paolo|last5=Rizzuto|first5=Rosario|last6=Rugolo|first6=Michela|date=2005-01-28|title=pH difference across the outer mitochondrial membrane measured with a green fluorescent protein mutant|journal=Biochemical and Biophysical Research Communications|volume=326|issue=4|pages=799–804|doi=10.1016/j.bbrc.2004.11.105|pmid=15607740}}</ref> 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 ==

=== Metabolites ===
The matrix is host to a wide variety of [[metabolite]]s involved in processes within the matrix. The [[citric acid cycle]] involves [[acyl-CoA]], [[pyruvate]], [[acetyl-CoA]], [[citrate]], [[isocitrate]], [[α-ketoglutarate]], [[succinyl-CoA]], [[fumarate]], [[succinate]], [[malate|<small>L</small>-malate]], and [[oxaloacetate]].<ref name=":1" /> The [[urea cycle]] makes use of [[ornithine|<small>L</small>-ornithine]], [[Carbamoyl phosphate synthetase I|carbamoyl phosphate]], and [[L-citrulline|<small>L</small>-citrulline]].<ref name=":5" /> The electron transport chain oxidizes coenzymes [[NADH]] and [[FADH2]]. Protein synthesis makes use of mitochondrial [[DNA]], [[RNA]], and [[Transfer RNA|tRNA]].<ref name=":6" /> Regulation of processes makes use of ions ([[Ca2+|Ca<sup>2+</sup>]]/[[Potassium|K<sup>+</sup>]]/[[Magnesium|Mg<sup>+</sup>]]).<ref name=":4" /> Additional metabolites present in the matrix are [[CO2|CO<sub>2</sub>]]<sub>,</sub> [[H2O|H<sub>2</sub>O]], [[Oxygen|O<sub>2</sub>]]<sub>,</sub> [[Adenosine triphosphate|ATP]], [[Adenosine diphosphate|ADP]], and [[Inorganic phosphate|P<sub>i</sub>]].<ref name=":0" />

=== Enzymes ===
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 coenzyme A synthetase|succinyl-CoA synthetase]], [[fumarase]], and [[malate dehydrogenase]].<ref name=":1" /> The urea cycle is facilitated by [[carbamoyl phosphate synthetase I]] and [[ornithine transcarbamylase]].<ref name=":5" /> β-Oxidation uses [[pyruvate carboxylase]], [[Acyl CoA dehydrogenase|acyl-CoA dehydrogenase]], and [[β-ketothiolase]].<ref name=":0" /> Amino acid production is facilitated by [[transaminase]]s.<ref name=":7" /> Amino acid metabolism is mediated by [[protease]]s, such as [[PITRM1|presequence protease]].<ref>{{Cite journal|last1=King|first1=John V.|last2=Liang|first2=Wenguang G.|last3=Scherpelz|first3=Kathryn P.|last4=Schilling|first4=Alexander B.|last5=Meredith|first5=Stephen C.|last6=Tang|first6=Wei-Jen|date=2014-07-08|title=Molecular basis of substrate recognition and degradation by human presequence protease|journal=Structure|volume=22|issue=7|pages=996–1007|doi=10.1016/j.str.2014.05.003|issn=1878-4186|pmc=4128088|pmid=24931469}}</ref>

=== Inner membrane components ===
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 [[crista]]e 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).<ref name=":4" />

=== Inner membrane control over matrix composition ===
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|Ca<sup>2+</sup>]] driven by the mitochondrial membrane potential.<ref name=":0" /> The membrane only allows nonpolar molecules such as [[Carbon dioxide|CO<sub>2</sub>]] and [[Oxygen|O<sub>2</sub>]] and small non charged polar molecules such as [[H2O|H<sub>2</sub>O]] to enter the matrix. Molecules enter and exit the mitochondrial matrix through [[transport protein]]s and [[ion transporter]]s. Molecules are then able to leave the mitochondria through [[Porin (protein)|porin]].<ref name=":2">{{Cite book|title=Molecular Biology of the Cell|last1=Alberts|first1=Bruce|last2=Johnson|first2=Alexander|last3=Lewis|first3=julian|last4=Roberts|first4=Keith|last5=Peters|first5=Walter|last6=Raff|first6=Martin|publisher=Garland Publishing Inc|year=1994|isbn=978-0-8153-3218-3|location=New york}}</ref> These attributed characteristics allow for control over concentrations of [[ion]]s and [[metabolite]]s necessary for regulation and determines the rate of ATP production.<ref>{{Cite journal|last1=Anderson|first1=S.|last2=Bankier|first2=A. T.|last3=Barrell|first3=B. G.|last4=de Bruijn|first4=M. H. L.|last5=Coulson|first5=A. R.|last6=Drouin|first6=J.|last7=Eperon|first7=I. C.|last8=Nierlich|first8=D. P.|last9=Roe|first9=B. A.|date=1981-04-09|title=Sequence and organization of the human mitochondrial genome|journal=Nature|language=en|volume=290|issue=5806|pages=457–465|doi=10.1038/290457a0|pmid=7219534|bibcode=1981Natur.290..457A |s2cid=4355527 }}</ref><ref name=":3">{{Cite journal|last1=Iuchi|first1=S.|last2=Lin|first2=E. C. C.|date=1993-07-01|title=Adaptation of Escherichia coli to redox environments by gene expression|journal=Molecular Microbiology|language=en|volume=9|issue=1|pages=9–15|doi=10.1111/j.1365-2958.1993.tb01664.x|issn=1365-2958|pmid=8412675|s2cid=39165641 }}</ref>

== Processes ==

=== Citric acid cycle ===
Following glycolysis, the citric acid cycle is activated by the production of acetyl-CoA. The oxidation of [[Pyruvic acid|pyruvate]] by pyruvate dehydrogenase in the matrix produces CO<sub>2</sub>, acetyl-CoA, and NADH. [[Beta oxidation]] of fatty acids serves as an alternate [[Catabolism|catabolic]] pathway that produces acetyl-CoA, NADH, and [[Flavin adenine dinucleotide|FADH<sub>2</sub>]].<ref name=":0" /> The production of acetyl-CoA begins the citric acid cycle while the [[Cofactor (biochemistry)|co-enzymes]] produced are used in the [[electron transport chain]].<ref name=":3" />[[File:Mitochondrial electron transport chain—Etc4.svg|thumb|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 [[enzyme]]s for the citric acid cycle are in the matrix (e.g. ''[[Citrate|citrate synthase]], [[isocitrate dehydrogenase]], [[Alpha-Ketoglutaric acid|α-ketoglutarate dehydrogenase]], [[Fumarate|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 FADH<sub>2</sub> through the oxidation of carbons in two cycles. The oxidation of NADH and FADH<sub>2</sub> produces GTP from succinyl-CoA synthetase.<ref name=":1" />

=== Oxidative phosphorylation ===
NADH and [[Flavin adenine dinucleotide|FADH<sub>2</sub>]] are produced in the matrix or transported in through porin and transport proteins in order to undergo oxidation through oxidative phosphorylation.<ref name=":0" /> NADH and FADH<sub>2</sub> undergo oxidation in the electron transport chain by transferring an [[electron]]s to regenerate [[NAD+|NAD<sup>+</sup>]] and [[Flavin adenine dinucleotide|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.<ref name=":4">{{Cite journal|last1=Dimroth|first1=P.|last2=Kaim|first2=G.|last3=Matthey|first3=U.|date=2000-01-01|title=Crucial role of the membrane potential for ATP synthesis by F(1)F(o) ATP synthases|journal=The Journal of Experimental Biology|volume=203|issue=Pt 1|pages=51–59|doi=10.1242/jeb.203.1.51 |issn=0022-0949|pmid=10600673|bibcode=2000JExpB.203...51D }}</ref>

=== Urea cycle ===
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.<ref>{{Cite journal|last1=Tuchman|first1=Mendel|last2=Plante|first2=Robert J.|date=1995-01-01|title=Mutations and polymorphisms in the human ornithine transcarbamylase gene: Mutation update addendum|journal=Human Mutation|language=en|volume=5|issue=4|pages=293–295|doi=10.1002/humu.1380050404|issn=1098-1004|pmid=7627182|s2cid=2951786 |doi-access=free}}</ref>

=== Transamination ===
[[Alpha-Ketoglutaric acid|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.<ref name=":7">{{Cite journal|last1=Karmen|first1=A.|last2=Wroblewski|first2=F.|last3=Ladue|first3=J. S.|date=1955-01-01|title=Transaminase activity in human blood|journal=The Journal of Clinical Investigation|volume=34|issue=1|pages=126–131|doi=10.1172/JCI103055|issn=0021-9738|pmc=438594|pmid=13221663}}</ref><ref>{{Cite journal|last1=Kirsch|first1=Jack F.|last2=Eichele|first2=Gregor|last3=Ford|first3=Geoffrey C.|last4=Vincent|first4=Michael G.|last5=Jansonius|first5=Johan N.|author-link5=Johan Jansonius|last6=Gehring|first6=Heinz|last7=Christen|first7=Philipp|date=1984-04-15|title=Mechanism of action of aspartate aminotransferase proposed on the basis of its spatial structure|journal=Journal of Molecular Biology|volume=174|issue=3|pages=497–525|doi=10.1016/0022-2836(84)90333-4|pmid=6143829}}</ref>

=== Regulation ===
Regulation within the matrix is primarily controlled by ion concentration, metabolite concentration and energy charge. Availability of ions such as [[Calcium signaling|Ca<sup>2+</sup> 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.<ref>{{Cite journal|last1=Denton|first1=Richard M.|last2=Randle|first2=Philip J.|last3=Bridges|first3=Barbara J.|last4=Cooper|first4=Ronald H.|last5=Kerbey|first5=Alan L.|last6=Pask|first6=Helen T.|last7=Severson|first7=David L.|last8=Stansbie|first8=David|last9=Whitehouse|first9=Susan|date=1975-10-01|title=Regulation of mammalian pyruvate dehydrogenase|journal=Molecular and Cellular Biochemistry|language=en|volume=9|issue=1|pages=27–53|doi=10.1007/BF01731731|issn=0300-8177|pmid=171557|s2cid=27367543 }}</ref> Concentration of intermediates and coenzymes in the matrix also increase or decrease the rate of ATP production due to [[Anaplerotic reactions|anaplerotic]] and cataplerotic effects. NADH can act as an [[Enzyme inhibitor|inhibitor]] for [[Alpha-Ketoglutaric acid|α-ketoglutarate]], [[isocitrate dehydrogenase]], [[citrate synthase]], and [[Pyruvate dehydrogenase complex|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.<ref name=":1" />  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 [[Enzyme activator|activator]].<ref name=":0" />

=== Protein synthesis ===
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 protein]]s, [[ribosomal RNA]], [[transfer RNA]], and [[protein subunit]]s found in the [[Multiprotein complex|protein complexes]] of the electron transport chain.<ref>{{Cite journal|last=Fox|first=Thomas D.|date=2012-12-01|title=Mitochondrial Protein Synthesis, Import, and Assembly|journal=Genetics|volume=192|issue=4|pages=1203–1234|doi=10.1534/genetics.112.141267|issn=0016-6731|pmc=3512135|pmid=23212899}}</ref><ref>{{Cite journal|last1=Grivell|first1=L.A.|last2=Pel|first2=H.J.|year=1994|title=Protein synthesis in mitochondria|url=https://pure.uva.nl/ws/files/2967481/358_4203y.pdf|journal=Mol. Biol. Rep.|volume=19|issue=3|doi=10.1007/bf00986960|pages=183–194|pmid=7969106 |s2cid=21200502 }}</ref>

==See also==
* [[Matrix (biology)]]
* [[Mitochondrial DNA]]
* [[Mitochondrion]]

==References==
{{Reflist}}

{{Mitochondrial enzymes}}

{{DEFAULTSORT:Mitochondrial Matrix}}
[[Category:Cell anatomy]]
[[Category:Matrices (biology)]]