NDUFA4

The protein encoded by this gene belongs to the complex I 9kDa subunit family. Mammalian complex I of mitochondrial respiratory chain is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq]

Full Name

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa

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 unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix (PubMed:22902835).

NDUFA4 is required for complex IV maintenance (PubMed:22902835).

Biological Process

Cellular respiration Source: ComplexPortal
Mitochondrial electron transport, cytochrome c to oxygen Source: ComplexPortal
Mitochondrial electron transport, NADH to ubiquinone Source: UniProtKB
Positive regulation of cytochrome-c oxidase activity Source: UniProtKB

Cellular Location

Mitochondrion inner membrane

Involvement in disease

Mitochondrial complex IV deficiency, nuclear type 21 (MC4DN21):
An autosomal recessive mitochondrial disorder with onset in infancy. MC4DN21 is characterized by congenital lactic acidosis, encephalopathy, global developmental delay, delayed speech, motor dysfunction, dystonia, and spasticity. Ataxia, peripheral neuropathy, and seizures may also occur. Patient tissues show variably decreased levels and activity of mitochondrial respiratory complex IV.

Topology

Mitochondrial matrix: 1-14
Helical: 15-37
Mitochondrial intermembrane: 38-81