COX4I1

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 16

MC4DN16

An autosomal recessive mitochondrial disorder with onset in infancy and variable manifestations. MC4DN16 features include feeding difficulties, poor overall growth, short stature, microcephaly, developmental regression, severe hypotonia, and seizures. Cerebral and cerebellar atrophy, and abnormal lesions in the basal ganglia can be observed on brain imaging. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.

None

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

Energy metabolism; oxidative phosphorylation.

Belongs to the cytochrome c oxidase IV family.

Ubiquitous.

• Mitochondrion inner membrane
• Single-pass membrane protein

COX4, COX4I1, Cytochrome c oxidase polypeptide IV, Cytochrome c oxidase subunit IV isoform 1, COX IV-1

• entrezGene:84701
• entrezGene:1327
• omim:607976
• omim:123864
• swissprot:P13073
• swissprot:Q96KJ9

Proteins

Metabolism

19577Da