COX18

Cox18 is a conserved mitochondrial inner-membrane protein that functions as an assembly factor for cytochrome c oxidase (Complex IV) of the mitochondrial respiratory chain. It is encoded by the COX18 gene in humans and has orthologs across diverse eukaryotes, indicating an ancient role in mitochondrial biogenesis. The protein is typically small and hydrophobic, predicted to contain a single transmembrane helix that anchors it to the inner mitochondrial membrane, with the exact import orientation varying by species.

In organisms where it has been studied, Cox18 participates in the biogenesis and/or stabilization of Complex IV during assembly, interacting with other assembly factors and subunits to promote correct incorporation of catalytic components. It is not considered a catalytic subunit of Complex IV. Loss or impairment of Cox18 function can lead to defects in Complex IV assembly and reduced respiratory activity, though the precise mechanism and the resulting phenotypes can differ between species.

Clinical relevance in humans is an area of ongoing research. Some studies have identified COX18 variants in patients with mitochondrial disease–related phenotypes, but causal relationships and the extent of their contribution remain to be established. Further work is needed to clarify the exact role, interacting partners, and regulation of Cox18 in mitochondrial biogenesis.

See also: Cytochrome c oxidase, Mitochondrial biogenesis, Assembly factors for respiratory complexes.