MOTS-c — Canada Research Brief
MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene, studied preclinically for AMPK signalling, glucose homeostasis, and metabolic adaptation to exercise.
Key facts
| Canonical name | MOTS-c |
|---|---|
| Alternate names | Mitochondrial open reading frame of the 12S rRNA type-c, MOTSc |
| Drug class | Mitochondrial-derived peptide (metabolic signalling) |
| CAS number | 1627580-64-6 |
| Molecular formula | C100H152N24O22S |
| Molecular weight | 2174.58 g/mol |
| Sequence | Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg |
Discovery and context
MOTS-c was identified by Changhan Lee and colleagues at USC in 2015 through systematic bioinformatic scanning of the mitochondrial 12S rRNA gene for small open reading frames (sORFs). They then synthesised the predicted peptide, demonstrated its presence in human plasma, and reported its metabolic effects in mice on a high-fat diet.
The broader context is the emerging concept of mitochondrial-derived peptides (MDPs) — short peptides translated from mitochondrial DNA sORFs that act as signalling molecules between mitochondria and the nucleus. Humanin was the first MDP identified; MOTS-c, SHLPs, and others followed.
Preclinical pathways
- AMPK activation. MOTS-c treatment has been reported to activate the AMPK pathway in skeletal muscle and adipose tissue, producing effects that resemble the metabolic signature of exercise — improved glucose uptake, fatty-acid oxidation, and mitochondrial biogenesis.
- Insulin sensitisation. In diet-induced obese mice and in age-related insulin resistance models, MOTS-c has been shown to improve insulin sensitivity and glucose tolerance.
- Exercise adaptation. Reynolds et al. (Nature Communications 2021) reported that MOTS-c levels rise with exercise and that exogenous MOTS-c preserves physical performance in ageing mice.
Storage
Store lyophilised MOTS-c at −20°C. Once reconstituted, refrigerate at 2–8°C and use within 2–4 weeks.
Frequently asked questions
What is MOTS-c?
How was MOTS-c discovered?
What pathways does MOTS-c affect?
What is MOTS-c's molecular weight?
References
- [1]Lee C, Zeng J, Drew BG, et al.. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 2015. DOI: 10.1016/j.cmet.2015.02.009
- [2]Reynolds JC, Lai RW, Woodhead JST, et al.. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline. Nature Communications, 2021. PMID: 33658471
- [3]National Center for Biotechnology Information. PubChem CID 91826424 — MOTS-c, 2024