Cytochrome c oxidase subunit 4 isoform 1, mitochondrial

COX4I1 encodes cytochrome c oxidase subunit 4 isoform 1, a core structural component of Complex IV (cytochrome c oxidase) in the mitochondrial electron transport chain. This enzyme catalyzes the final step of oxidative phosphorylation, accepting electrons from cytochrome c and reducing molecular oxygen to water while simultaneously pumping protons across the inner mitochondrial membrane (UniProt: P13073).

COX4I1 is expressed in tissues with high oxidative metabolism, particularly the brain and muscle. Pathogenic variants cause mitochondrial complex IV deficiency, nuclear type 16 (MC4DN16), a severe autosomal recessive disorder presenting in infancy with developmental regression, seizures, and neurodegeneration (UniProt: P13073).

COX4I1 is upregulated in Alzheimer's disease brain tissue relative to age-matched controls (Chaparral AD proteomics). The protein shows a mean log2 fold-change of 1.89 across post-mortem AD brain fractions measured by tandem mass spectrometry. This elevation may reflect compensatory increases in mitochondrial oxidative capacity or altered metabolic demands in AD pathology, though the functional significance remains to be established.