MOTS-c
Mitochondrial-encoded exercise mimetic — activates AMPK, improves insulin sensitivity, and drives mitochondrial biogenesis.
Research facts
| Half-life | ~2–3h |
|---|---|
| Route | SubQ |
| Typical dose | 5–10 mg/week |
| Frequency | 2–3× weekly |
| Solvent | Bacteriostatic water |
| pH | 5.5–7.0 |
| Stability | 30 days at +4°C |
Mechanism of action
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial 12S ribosomal RNA — one of the newly discovered class of mitochondria-derived peptides. It activates AMPK (AMP-activated protein kinase) and FOXO transcription factors, driving metabolic gene programmes that mimic the molecular response to exercise. In skeletal muscle, MOTS-c increases GLUT-4 expression, glucose uptake, and fatty acid oxidation. It also promotes mitochondrial biogenesis via PGC-1α upregulation. Injection of MOTS-c in obese mice restores insulin sensitivity and prevents diet-induced obesity. Exercise itself increases circulating MOTS-c levels, suggesting it may mediate some metabolic benefits of physical activity.
Documented effects (research-model)
- AMPK activation mimicking exercise metabolic signalling
- Insulin sensitivity improvement (GLUT-4 upregulation)
- Mitochondrial biogenesis via PGC-1α
- Fatty acid oxidation enhancement
- Anti-obesity effects in animal models
- Exercise mimetic properties — potential for metabolic-compromised populations
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| Standard | 5 mg 2×/week SubQ | Twice weekly | 8–12 weeks | 10mg / 2mL BAC water |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- Humanin HIGH
Both mitochondria-encoded peptides — Humanin is cytoprotective; MOTS-c drives metabolic adaptation. Complementary. - SS-31 HIGH
SS-31 stabilises mitochondrial membranes; MOTS-c drives biogenesis. Comprehensive mitochondrial protocol. - NAD+ HIGH
NAD+ provides metabolic substrate; MOTS-c drives the adaptive signalling. Synergistic mitochondrial support.
Myths & misconceptions
Evidence gaps
- All efficacy data from animal models. No completed human RCTs for metabolic or body composition outcomes.
- Optimal dose and schedule for human metabolic effects entirely unknown.
- Whether exogenous MOTS-c crosses the blood-brain barrier to exert neuro effects in humans is uncharacterised.
Safety notes
Very limited human safety data. Animal studies show favourable metabolic effects without toxicity. Proceed with caution; this is a cutting-edge research area with minimal human pharmacological characterisation.
Biomarkers to monitor
Primary-source citations
- PMID 25738459 — MOTS-c: A mitochondrial-derived peptide regulates insulin sensitivity (Cell Metab. 2015)
Frequently asked
What is MOTS-c?
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c Peptide) is a research compound classified in our library as Tier D — Animal or in-vitro data only.. Mitochondrial-encoded exercise mimetic — activates AMPK, improves insulin sensitivity, and drives mitochondrial biogenesis.
What is the evidence tier for MOTS-c?
We classify MOTS-c as Tier D: Animal or in-vitro data only. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of MOTS-c?
For MOTS-c, typical research dose is 5–10 mg/week, route is SubQ, half-life is ~2–3h. Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
What does MOTS-c stack well with?
MOTS-c stacks well with Humanin. Both mitochondria-encoded peptides — Humanin is cytoprotective; MOTS-c drives metabolic adaptation. Complementary.
Is MOTS-c safe?
Very limited human safety data. Animal studies show favourable metabolic effects without toxicity. Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.