MOTS-c
Mitochondrial ORF of the 12S rRNA Type-c
16-aa mitochondrial ORF peptide (MDP). Lee 2015 AMPK/metabolic papers are real. Not metformin, not an obesity RCT, not exercise in a vial. Community mg schedules are scaled from rodents, not a label.
Use-case scores
0–10 against the evidence we have, not a gym ranking. Hidden domains do not apply here.
- Metabolic / weight3.5/10
Lee 2015 (PMID 25738459) is Cell Metabolism: circulating MOTS-c, AMPK, mouse metabolic work. Not an obesity RCT. Community/small-human ceiling after haircut: 3.5.
- Longevity / aging2/10
Mitokine story. Lifespan headlines are preclinical. Mechanism band.
Compound card
- Sequence
- MRWQEMGYIFYPRKLR
- Class
- Mitochondrial ORF peptide (16 aa; MDP)
- Formula
- MTNIRTLSRS... (16 aa mitochondrial peptide)
- Status
- Not FDA-approved · research use
How it works
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a mitochondrial-derived peptide (MDP) - a signaling molecule encoded in the mitochondrial genome rather than the nuclear genome. It activates the AMPK pathway, the master metabolic regulator that enhances cellular energy metabolism, improves insulin sensitivity, and promotes glucose uptake in skeletal muscle.
MOTS-c represents a new class of signaling molecules called "mitokines" - mitochondrial hormones that communicate metabolic status from mitochondria to the nucleus and distant tissues. It has shown exercise-mimetic effects, improving metabolic health and physical performance in animal models.
Source: PMID: 25738459
Goal context
Exercise mimetic is a paper genre
AMPK activation in mice is not a VO2max trial. Train anyway.
Background & History
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene, discovered by Changhan David Lee at USC in 2015 (Cell Metabolism). It was the first regulatory peptide found to be encoded in mitochondrial DNA rather than nuclear DNA - a paradigm shift in mitochondrial biology. MOTS-c acts as a retrograde signal from mitochondria to the nucleus, activating AMPK and regulating metabolic gene expression. Exercise increases circulating MOTS-c levels, suggesting it mediates some of the metabolic benefits of physical activity.
Research Use Cases
- ✓Identity: 16-aa mtDNA ORF vs MOTS-c marketing
- ✓AMPK papers vs an obesity RCT (there is not one)
- ✓Not metformin and not an exercise replacement
Dosing
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Standard Protocol | 5 - 10 mg | 3-5x per week (SC) | 16-hour half-life supports intermittent dosing. Most rodent research used 5 mg/kg. |
Administration
Timeline
Who it is for
Metabolic Optimization
ModerateAMPK activation improves glucose metabolism and insulin sensitivity. Exercise-mimetic properties.
Longevity / Anti-Aging
LowPromising mitokine signaling in animal models. Human data is very limited.
Reconstitution
| Vial | Water | Concentration | Example dose |
|---|---|---|---|
| 5 mg lyophilized | 2 mL BAC | 2.5 mg/mL | 5 mg / 2 mL = 2.5 mg/mL. 5 mg = 2.0 mL = 200 units. Split across the week; do not treat rodent mg/kg as a human label. |
Change vial size or water volume? Open the reconstitution calculator.
Safety & Considerations
Research peptide. Limited human safety data - primarily rodent models. Naturally occurring endogenous mitochondrial peptide. Monitor blood glucose if diabetic.
Regulatory & Legal Status
Not currently on the WADA 2026 Prohibited List. Policies may change - verify before competition.
Research Chemical
US Compounding: Not eligible / not available
⚠️ This information is for educational purposes only and may not reflect the most current regulatory updates. Always verify with official FDA, WADA, and jurisdiction-specific sources before use.
Limits of current evidence
- Rodent mg/kg does not become 5–10 mg three times a week as a fact. That is community scaling.
- Half-life figures on vendor cards are estimates. Human PK is thin.
- This site will not treat diabetes or obesity from a MOTS-c page.
Human evidence
Low · mitokine papers, thin human PK
- Lee 2015 and related MDP work are metabolic/animal-heavy; not an obesity or diabetes RCT label.
- Human PK is thin. Vendor half-life cards are estimates.
- Rodent mg/kg does not become a sourced human titration chart.
Verdict
MOTS-c is a 16-aa peptide encoded in mtDNA. AMPK-linked metabolic papers exist. It is not an exercise-in-a-vial drug, not metformin, and not a type-2-diabetes indication.
Interactions & Contraindications
Research compound - limited human safety data. AMPK activation may interact with metformin (additive effects on glucose metabolism). Caution with insulin or GLP-1 agonists due to additive insulin sensitization. Available in injectable form; oral bioavailability very limited.
Synergies & Common Stacks
Both are mitochondrial-derived peptides (MDPs) with overlapping cytoprotective effects. Humanin protects against apoptosis; MOTS-c enhances metabolic function. Often combined in mitochondrial health protocols.
NAD+ is a cofactor. MOTS-c is an mtDNA ORF with AMPK papers. Complementary marketing is not a mitochondrial-resilience RCT.
Appears in goal guides
Goal guides are maps, not clinic protocols. A mention here is not a treatment plan.
Perimenopause & Menopause Optimization
Kisspeptin, Epitalon, MOTS-c, and PT-141 as they show up next to menopause folklore. Not HRT and not a vasomotor-symptom indication.
Weight Loss Plateau Breakthrough
Tesamorelin VAT label versus off-label secretagogue folklore. Visceral fat that “refuses to burn” is not a research-chem indication.
Ultimate Athletic Performance
Muscle and vascular cytomax plus BPC-157/TB-500 and GH secretagogues as they show up in athletic folklore. Injectable repair peptides are WADA-prohibited. This is not a doping pass.
Anti-Aging Longevity Stack
Golden Triangle (Endoluten, Vladonix, Bonomarlot) plus Epitalon and GHK-Cu, with FOXO4-DRI and MOTS-c as experimental add-ons.
Centenarian Decathlon Prep
Healthspan stack for muscle, cartilage, and VO2: Gotratix, Sigumir, Ventfort, plus MOTS-c. Inspired by Attia's marginal-decade idea, not a guarantee you die at 50 in a gym.
Frequently Asked Questions
What does MOTS-c do?▼
How is MOTS-c dosed?▼
References
- Reynolds JC et al. “"MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline".” Nature Communications (2021). PMID: 33594076
- Reynolds JC, et al. “MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline.” Nat Commun (2021). PMID: 33479227
- Lee C, et al. “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis.” Cell Metab (2015). PMID: 25738456
📚 Related Articles
Get MOTS-c from our recommended source - independently tested, COA-verified, USP <85> endotoxin compliant. Use code 4SS6SFTUGB at checkout.
Affiliate link · Full review