Cytochrome c oxidase subunit 5A, mitochondrial

COX5A encodes cytochrome c oxidase subunit 5A, a component of the mitochondrial respiratory chain complex IV that catalyzes the reduction of oxygen to water (UniProt: P20674). It participates in the electron transfer cascade that generates the proton gradient essential for ATP synthesis, with electrons flowing through dinuclear copper and heme centers to reduce molecular oxygen.

The protein is expressed in tissues dependent on oxidative phosphorylation. Genetic mutations in COX5A cause mitochondrial complex IV deficiency, nuclear type 20 (MC4DN20), a severe autosomal recessive disorder presenting in infancy with pulmonary hypertension, failure to thrive, hypotonia, and cardiorespiratory complications (UniProt: P20674).

COX5A is downregulated in post-mortem Alzheimer's disease brain tissue relative to age-matched controls, with a mean log₂ fold-change of −0.67 in human TMT proteomics (Chaparral AD proteomics). This reduction in a critical mitochondrial enzyme suggests impaired oxidative capacity in AD brain, consistent with documented mitochondrial dysfunction in Alzheimer's pathology.