MT-CO3

MT-CO3 (Mitochondrially Encoded Cytochrome C Oxidase III) is a Protein Coding gene. Diseases associated with MT-CO3 include Leber Hereditary Optic Neuropathy and Genetic Recurrent Myoglobinuria. Among its related pathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Gene Expression. Gene Ontology (GO) annotations related to this gene include cytochrome-c oxidase activity and heme-copper terminal oxidase activity.

Full Name

MITOCHONDRIALLY ENCODED CYTOCHROME C OXIDASE III

Function

Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.

Biological Process

Aerobic respiration Source: GO_Central
Cellular respiration Source: ComplexPortal
Mitochondrial electron transport, cytochrome c to oxygen Source: GO_Central
Respiratory chain complex IV assembly Source: UniProtKB

Cellular Location

Mitochondrion inner membrane

Involvement in disease

Leber hereditary optic neuropathy (LHON):
A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Mitochondrial complex IV deficiency (MT-C4D):
A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome.
Recurrent myoglobinuria mitochondrial (RM-MT):
Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness, and followed by excretion of myoglobin in the urine.

Topology

Mitochondrial matrix: 1-15
Helical: 16-34
Mitochondrial intermembrane: 35-40
Helical: 41-66
Mitochondrial matrix: 67-72
Helical: 73-105
Mitochondrial intermembrane: 106-128
Helical: 129-152
Mitochondrial matrix: 153-155
Helical: 156-183
Mitochondrial intermembrane: 184-190
Helical: 191-223
Mitochondrial matrix: 224-232
Helical: 233-256
Mitochondrial intermembrane: 257-261