Cytochrome c oxidase subunit 6B1

COX6B1 (cytochrome c oxidase subunit 6B1) is a small mitochondrial protein that functions as a component of cytochrome c oxidase (complex IV), the terminal enzyme of the electron transport chain. It participates in the final step of oxidative phosphorylation by facilitating electron transfer to molecular oxygen, generating the proton gradient essential for ATP synthesis (UniProt: P14854).

COX6B1 is localized to the inner mitochondrial membrane and operates within the broader context of aerobic metabolism. Mutations in COX6B1 cause mitochondrial complex IV deficiency, nuclear type 7 (MC4DN7), a rare autosomal recessive disorder presenting with encephalomyopathy, neurodegeneration, cognitive decline, and cardiac involvement (UniProt: P14854).

In Alzheimer's disease, COX6B1 is down-regulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.35 (Chaparral AD proteomics). This reduction in a critical oxidative phosphorylation component suggests compromised mitochondrial electron transport capacity in AD, consistent with the bioenergetic deficits implicated in AD pathology.