COX8A

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.

Mitochondrial complex IV deficiency, nuclear type 15

MC4DN15

An autosomal recessive mitochondrial disorder with onset in infancy. MC4DN15 is characterized by global developmental delay, poor feeding, metabolic acidosis, short stature, microcephaly, proximal muscle weakness, and distal spasticity. Additional manifestations include scoliosis, primary pulmonary hypertension, refractory seizures, and inability to walk. Serum and CSF lactate levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.

None

The disease may be caused by variants affecting the gene represented in this entry.

Energy metabolism; oxidative phosphorylation.

In response to mitochondrial stress, the precursor protein is ubiquitinated by the SIFI complex in the cytoplasm before mitochondrial import, leading to its degradation (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121).

Belongs to the cytochrome c oxidase VIII family.

Widely expressed.

• Mitochondrion inner membrane
• Single-pass membrane protein

COX8, COX8L, COX8A, Cytochrome c oxidase polypeptide VIII-liver/heart, Cytochrome c oxidase subunit 8-2

• entrezGene:1351
• omim:123870
• swissprot:P10176

Proteins

Metabolism

7579Da