MOTS-c

MOTS-c (Mitochondrial Open Reading frame of the Twelve S rRNA-c) is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA — one of a small group of "mitochondrial-derived peptides" expressed from the mitochondrial genome itself rather than the nuclear genome.

The peptide acts as a mitochondrial-to-nucleus retrograde signaling molecule. In skeletal muscle, MOTS-c activates AMP-activated protein kinase (AMPK), promotes glucose uptake, and modulates folate-methionine cycle metabolism. Translocation to the nucleus under metabolic stress engages adaptive transcriptional programs, positioning the peptide as a mitochondrial sensor of cellular energy state.

Circulating MOTS-c declines with age in human plasma — an observation that has shaped a research interest in geroscience and metabolic-aging contexts.

Research Applications

• AMPK pathway and skeletal muscle metabolic research.
• Mitochondrial retrograde signaling and mitonuclear communication studies.
• Geroscience research on age-related metabolic decline.
• Exercise physiology and insulin sensitivity research.