The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance

First description of MOTS-c, a 16 amino acid peptide from a reading frame of the mitochondrial 12S rRNA gene. In cells it inhibits the folate cycle and activates AMPK; in mice it prevented diet-induced obesity and insulin resistance.

Key points

• MOTS-c is encoded in the mitochondrial genome, in a short reading frame within the 12S rRNA gene.
• The peptide inhibits the folate cycle and the coupled purine synthesis; AICAR accumulates and AMPK is activated.
• The main target organ is skeletal muscle. In mice, MOTS-c prevented obesity and insulin resistance induced by a high-fat diet, as well as age-related insulin resistance.

Assessment

Evidence type: preclinical. The foundational paper that all later MOTS-c research refers to. All effect findings come from cell culture and mouse models. Profile: MOTS-c.