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MOTS-c (Mitochondrial ORF of the 12S rRNA type-c) is a 16-amino-acid peptide encoded not in nuclear DNA but within the mitochondrial genome itself - specifically in a short open reading frame inside the 12S ribosomal RNA gene. It belongs to a small class known as mitochondrial-derived peptides, discovered when researchers began systematically searching the mitochondrial genome for previously unannotated coding sequences.

Its defining feature is that it acts as a retrograde signal: a message sent from the mitochondrion outward to the rest of the cell and, once released into circulation, to other tissues. Published work associates MOTS-c with AMPK activation and with regulation of the folate-methionine one-carbon cycle, placing it upstream of cellular energy sensing and metabolic homeostasis. Circulating levels have been reported to rise acutely with exercise, which is why it appears in the literature described as an exercise-responsive peptide.

MOTS-c is a research compound with no marketing authorisation in any jurisdiction. Supplied in a 3 mL pre-filled pen at 5 mg/mL (15 mg total peptide).