Cytochrome c oxidase subunit 1 (mutated) (COX1)

Cytochrome c oxidase subunit 1 (COX1) is a mitochondrial-encoded enzyme that serves as the catalytic core of Complex IV in the electron transport chain, facilitating the reduction of oxygen to water (UniProt P00395). In the RENCA murine renal adenocarcinoma model, a specific somatic missense mutation (G6234A) in the mt-Co1 gene results in the production of a mutated protein that functions as a tumor-associated mitochondrial antigen (TAMA) (Pierini et al., 2015). This mutation creates a neoepitope, such as the COX1 291–306 peptide (MFTVGLDVDTRTYFT), which is presented by MHC Class I molecules to stimulate a potent cytotoxic T-lymphocyte (CTL) response (Facciabene et al., 2012). Therapeutic strategies targeting this mutated COX1, including dendritic cell-based vaccines and peptide vaccines, have demonstrated the ability to control tumor growth and improve survival, particularly when combined with immune checkpoint inhibitors like PD-1/PD-L1 blockade (Perales Linares et al., 2026). This target highlights the potential of the mitochondrial genome as a source of immunogenic neoantigens for personalized cancer therapy, though its efficacy can be limited by tumor-mediated immune evasion mechanisms such as the loss of Parkin-mediated antigen presentation (Perales Linares et al., 2026).

Other names

MT-CO1Cytochrome c oxidase subunit IComplex IV subunit 1Tumor-associated mitochondrial antigenTAMA

Induction of antigen-specific CD8+ T-lymphocyte responses against mutated mitochondrial epitopes presented on MHC Class I molecules.