Cytochrome c oxidase subunit 1 (MT-CO1) mutant peptide (MT-CO1 mutant peptide)

Cytochrome c oxidase subunit 1 (MT-CO1) is the primary catalytic subunit of Complex IV, the terminal enzyme of the mitochondrial respiratory chain that facilitates the transfer of electrons to oxygen (Source: UniProt P00395). Somatic mutations in the mitochondrial DNA (mtDNA) encoding MT-CO1 are prevalent in several cancer types, including prostate and colorectal carcinomas, leading to the synthesis of altered protein sequences (Source: PubMed 25803485). These mutant peptides can be processed by the proteasome and presented on the cell surface via Human Leukocyte Antigen (HLA) molecules, acting as tumor-specific neoantigens or mitoneoantigens (Source: PubMed 31534224). Because these mutations are often absent in healthy nuclear DNA and normal tissues, they represent attractive targets for precision immunotherapy, such as peptide-based vaccines and T-cell receptor (TCR) therapies (Source: PubMed 33009407). Targeting these peptides aims to trigger a robust cytotoxic T-cell response specifically against malignant cells harboring the mtDNA mutations. However, therapeutic development is complicated by mitochondrial heteroplasmy, where cells contain a mixture of mutant and wild-type mtDNA, potentially affecting the density of antigen presentation (Source: PubMed 29109393). This target class represents a novel frontier in oncology, leveraging the unique genetic landscape of the mitochondrial genome to overcome traditional tumor resistance mechanisms.

Other names

COX1 mutant peptideMT-CO1 neoantigenMitochondrial-encoded cytochrome c oxidase I mutant peptideMTCO1 mutant peptideMitochondrial neoantigenMitoneoantigen

Induction of cytotoxic T-lymphocyte (CTL) responses through the recognition of mutant mitochondrial peptides presented on MHC class I molecules.