Variants of it have been associated with isolated myopathy, severe encephalomyopathy, Leber hereditary optic neuropathy, mitochondrial complex IV deficiency, and recurrent myoglobinuria .

It catalyzes the transfer of electrons from reduced cytochrome c to molecular oxygen: This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane.

The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits, I, II and III.

[15][16][17] Mutations in mtDNA-encoded cytochrome c oxidase subunit genes have been observed to be associated with isolated myopathy, severe encephalomyopathy, Leber hereditary optic neuropathy, mitochondrial complex IV deficiency, and recurrent myoglobinuria .

[7][8][9] LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction.

Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development, mental retardation, lactic acidemia, encephalopathy, ataxia, and cardiac arrhythmia.