MOTS-c
A 16-residue peptide encoded within mitochondrial 12S rRNA. Studied as a regulator of metabolic homeostasis via AMPK, and as a mitochondrial-to-nuclear signalling molecule.
| Total citations | 4 |
|---|---|
| Human clinical studies | 1 |
| Animal models | 2 |
| In vitro studies | 1 |
| Reviews / meta-analyses | 0 |
Mechanism of action
MOTS-c (MRWQEMGYIFYPRKLR) is encoded in the mitochondrial genome. Lee and colleagues showed it targets the folate–methionine cycle, causing accumulation of AICAR and consequent AMPK activation, which shifts substrate use and improves insulin sensitivity in mice.
Kim and colleagues subsequently demonstrated that under metabolic stress it translocates to the nucleus and regulates nuclear gene expression, including antioxidant response element and stress-response genes — establishing bidirectional mitochondrial-to-nuclear signalling.
Peer-reviewed literature
Study type is tagged on every entry so animal and in-vitro findings are never mistaken for human clinical evidence.
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
The originating paper: identified MOTS-c and showed AMPK-mediated improvement in insulin sensitivity in mice.
The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress
Established nuclear translocation and regulation of stress-response gene programmes.
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
Reported effects on physical capacity in mice alongside measurements in human samples.
Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans
Observational human study showing endogenous MOTS-c rises acutely after endurance exercise.
Limitations & open questions
Human data is limited to observational measurement of endogenous circulating levels, for example after exercise. No human administration trials have been verified.