RT Journal Article SR Electronic T1 MTALTCO1: a 259 amino-acid long mtDNA-encoded alternative protein that challenges conventional understandings of mitochondrial genomics JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.09.22.614361 DO 10.1101/2024.09.22.614361 A1 Robitaille, Francis A1 Ben Hadj, Aziz A1 Campbell, Amy A1 Nadeau-Lachance, Ludovic A1 Niaison, Thierry A1 Choquette, Thierry A1 Roucou, Xavier A1 Angers, Annie A1 Breton, Sophie YR 2024 UL http://biorxiv.org/content/early/2024/09/30/2024.09.22.614361.abstract AB Mitochondrial-derived peptides significantly expand the coding potential of the human mitochondrial genome. Here, we report the discovery of MTALTCO1, a 259 amino-acid protein encoded by a mitochondrial alternative open reading frame found in the +3 reading frame of the cytochrome oxidase 1 gene (CO1). Using a custom antibody, we confirmed the mitochondrial expression of MTALTCO1 in human cell lines. Sequence analysis revealed high arginine content and an elevated isoelectric point that were not contingent on CO1’s amino acid sequence, suggesting selective pressures might be acting on this protein. MTALTCO1 displays extensive fusion-fission dynamics at the interspecies level, yet produces a full-length protein throughout human mitochondrial lineages. Our findings highlight the importance of identifying novel mitochondrial-derived peptides and proteins in expanding our understanding of the mitochondrial proteome.Competing Interest StatementThe authors have declared no competing interest.