Mitochondrial matrix

In a mitochondrion, the matrix is the space within the 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, 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.

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.

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. 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. 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 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. The urea cycle makes use of L-ornithine, carbamoyl phosphate, and L-citrulline. This enzyme system is organized as individual, matrix-soluble proteins, in contrast to the single, multi-domain enzyme FASN of cytosolic fatty acid synthesis.

Non-enzymatic proteins

Members of the superfamily of LYRM proteins – with the exception of LYRM3 and LYRM6, which are embedded in mitochondrial Complex I – are primarily soluble mitochondrial matrix proteins. They are involved in the assembly of electron transport chain complexes and mitochondrial ribosomes, as well as in iron–sulfur cluster biogenesis and the function of the electron-transfer flavoprotein (ETF).

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 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). These attributed characteristics allow for control over concentrations of ions and metabolites necessary for regulation and determines the rate of ATP production.

Processes

Citric acid cycle

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.

Mitochondrial fatty acid synthesis

thumb|Schematic representation of mitochondrial fatty acid synthesis (mtFAS), illustrating stepwise elongation of fatty acyl chains on mitochondrial acyl carrier protein (mtACP) and formation of acyl-mtACP species of varying chain length (e.g. octanoyl-, myristoyl-, and palmitoyl-mtACP).

In response to the availability of mitochondrial acetyl-CoA, mitochondrial fatty acid synthesis (mtFAS) produces fatty acyl chains. These are synthesized on the mitochondrial acyl carrier protein (mtACP), where they are elongated by two-carbon units in each cycle. By contrast, longer acyl-mtACP species allosterically regulate LYRM proteins, which are required for iron–sulfur cluster biogenesis, assembly of electron transport chain complexes, and the function of the electron-transfer flavoprotein (ETF).

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.

Transamination

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.

Regulation

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. 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.