MOTS-c — mitochondrial open reading frame of the 12S rRNA-c — is a short bioactive peptide whose coding sequence sits inside the mitochondrial DNA 12S ribosomal RNA gene rather than in the nuclear genome. Studied in metabolic-homeostasis, muscle and fat metabolism, and exercise-physiology preclinical models with AMPK-axis signalling as the dominant mechanistic finding.
Definition
MOTS-c is a 16-amino-acid peptide (sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg). What makes the peptide structurally unusual is that its coding sequence is located inside the mitochondrial genome — specifically within the 12S ribosomal RNA gene — rather than in the nuclear genome that encodes the great majority of mammalian peptide and protein sequences. That places MOTS-c in the small but growing class of mitochondrial-derived peptides (MDPs) alongside humanin and the SHLP family. The peptide was first characterised by Changhan Lee and colleagues in 2015, with the initial publication establishing its role as a metabolic regulator that promotes systemic insulin sensitivity and glucose homeostasis in mouse models (PMID 25738459).
MOTS-c is the only currently-characterised mitochondrial-derived peptide with substantial published research on systemic metabolic function. The peptide is produced from mitochondrial 12S rRNA reading-frame translation, is exported from the mitochondrion to the cytosol, and at physiological stress states translocates from the cytosol to the nucleus where it influences nuclear gene expression in response to metabolic-stress inputs (PMID 29983246).
How MOTS-c is studied in peptide research
The published mechanistic literature centres on AMPK (AMP-activated protein kinase) activation as the primary signalling cascade engaged by the peptide, with downstream effects on glucose uptake, fatty acid oxidation, and mitochondrial biogenesis programs. The follow-up Lee characterisation extended the metabolic-regulation framework specifically into muscle and adipose tissue contexts (PMID 27216708). The Kim nuclear-translocation work established the metabolic-stress-responsive translocation behaviour and the consequent regulation of nuclear gene expression programs (PMID 29983246).
Subsequent research has examined MOTS-c in exercise-physiology, ageing, and metabolic-disease contexts, with the peptide positioned as a candidate signalling molecule mediating systemic responses to exercise and caloric-restriction interventions. The published literature is comparatively young (first characterisation 2015) and the compound’s broader mechanism map continues to be elaborated by multiple research groups.
Related terms
- AMPK / AMP-activated protein kinase
- mTOR (downstream of AMPK)
- Mitochondrial-derived peptide (MDP)
- Humanin
- Mitochondrial 12S rRNA
- Insulin sensitivity
- Mitochondrial biogenesis
Where MOTS-c appears in the Ronin catalog
- MOTS-c 10mg — single-compound vial, lyophilized white powder under inert gas
References
- Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015;21(3):443-454. [PMID 25738459]
- Lee C et al. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med 2016;100:182-187. [PMID 27216708]
- Kim KH et al. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab 2018;28(3):516-524. [PMID 29983246]
Glossary entries describe research-context use of peptide-research terminology. They do not constitute medical, veterinary, or clinical advice. MOTS-c is sold strictly as a research-grade reagent for laboratory and bench research applications.