MOTS-c
Mitochondrial-derived peptide · MOTSc
Mitochondrial-derived peptide regulating metabolic homeostasis (preclinical)
Overview
MOTS-c (mitochondrial open reading frame of the twelve-S rRNA type-c) is a short peptide encoded within the mitochondrial genome rather than the nuclear genome. It was characterized by Lee and colleagues (Cell Metabolism, 2015), who described it as a mitochondrial-derived peptide that influences whole-body metabolism, in part by promoting AMP-activated protein kinase (AMPK) signaling and modulating the methionine–folate one-carbon pathway.
In rodent and cell-based studies, MOTS-c has been associated with improved insulin sensitivity, resistance to diet-induced obesity, and translocation to the nucleus under metabolic stress, where it is reported to influence the transcription of antioxidant and metabolic genes. Interest in the peptide for healthy-aging contexts stems from this proposed role as a mitochondrial-to-nuclear signaling molecule, though direct human longevity outcomes have not been demonstrated.
Human clinical data are limited. The doses and frequencies summarized here are community-derived rather than drawn from controlled human trials, and the peptide's pharmacokinetics in people are not well established. All figures should be treated as research reference only and verified against primary sources.
Key parameters
- Dose range
- 5–10 mg per dose (community)
- Frequency
- 2–3× weekly
- Half-life
- Not well characterized in humans (short, typical of small peptides)
- Route
- Subcutaneous
- Vial sizes
- 5 mg · 10 mg
- Regulatory status
- Not approved; research use only.
Mechanism of action
AMPK activation
Reported to stimulate AMP-activated protein kinase, a central energy sensor that promotes glucose uptake and fatty-acid oxidation when cellular energy is low.
Folate / one-carbon metabolism
Implicated in the methionine–folate cycle; metabolic stress is proposed to shift MOTS-c toward this pathway, linking it to AMPK signaling in preclinical models.
Mitochondrial-to-nuclear signaling
Under metabolic stress, MOTS-c is reported to translocate to the nucleus and influence stress-adaptive and antioxidant gene expression (preclinical observation).
Dosing protocol & phases
| Phase | Weeks | Dose | Notes |
|---|---|---|---|
| Standard (community) | Ongoing | 5–10 mg per dose, 2–3× weekly | Community-derived schedule; not clinically validated. |
Reconstitution guide
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.
5 mg vial + 2 mL bacteriostatic water
Concentration2,500 mcg/mL · 2.5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 2,500 mcg | 1 mL | 100 |
| 5,000 mcg | 2 mL | 200 |
Convenient mix for a single ~5 mg dose from a 5 mg vial.
10 mg vial + 3 mL bacteriostatic water
Concentration3,333.3 mcg/mL · 3.333 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 5,000 mcg | 1.5 mL | 150 |
| 10,000 mcg | 3 mL | 300 |
Higher-fill mix that keeps a 5 mg draw near half a milliliter while accommodating up to 10 mg.
Reconstitution calculator
Pre-filled with MOTS-c's vial sizes. Adjust the water volume and target dose to see the exact draw, with warnings for doses that are hard to measure or won't fit a syringe.
At 2,500 micrograms per millilitre, a 2,500 microgram dose is 1 millilitres, or 100 units on a U-100 syringe, giving 2 doses per vial.
This draw is 100 units, which won't fit in a 50-unit syringe. Use more bacteriostatic water (lower concentration) or split the dose.
Supplies needed
Affiliate disclosure: we may earn a commission from supplier links, at no extra cost to you. For research and educational use only.
Recommended supply
MOTS-c — research vial
From our verified partner Dynotides, with a third-party certificate of analysis per batch.
Injection supplies
- View
Bacteriostatic water
Diluent for reconstituting lyophilized vials.
- Buy
Insulin syringes (U-100)
0.3–0.5 mL, 29–31 G for accurate small draws.
- Buy
Alcohol prep pads
Sterile swabs for the vial stopper and site.
- Buy
Sharps container
Safe disposal of used needles.
- Buy
Storage fridge
Keeps reconstituted vials at 2–8 °C.
- Buy
Insulated travel case
Cooled, TSA-friendly case for travel.
Missed-dose guidance
No approved-label guidance exists because MOTS-c is not an approved drug. Community protocols typically resume the regular schedule at the next planned dose without doubling up.
Side effects & safety
| Category | Effect | Trial incidence |
|---|---|---|
| Injection site | Local reactions (redness, irritation)Anecdotal; no controlled human incidence data. | — |
| General | Fatigue or flushing reported anecdotallyCommunity reports only; human safety data are limited. | — |
Clinical trials & evidence
Lee et al. mechanistic characterization
Preclinical (animal/cell)Varies · Mouse models and cell lines
Characterized MOTS-c as a mitochondrial-derived peptide promoting AMPK signaling, improving insulin sensitivity, and resisting diet-induced obesity.
Trial identifier needs verification
Human efficacy / longevity trials
Not establishedN/A · N/A
No controlled human longevity trials identified; human dosing is community-derived.
Trial identifier needs verification
Storage & handling
- Lyophilized
- Refrigerate lyophilized powder at 2–8 °C, protected from light; for long-term storage a freezer (around −20 °C) is preferred.
- Reconstituted
- Refrigerate reconstituted solution at 2–8 °C and use within ~28 days; do not freeze.
Comparisons
| Vs. | Target | Half-life | Dosing | Efficacy | Status |
|---|---|---|---|---|---|
| Humanin | Mitochondrial-derived peptide (both) | Not characterized vs ~30 min (native) | Community-derived (both) | Both preclinical; distinct emphases (metabolic vs cytoprotective) | Both not approved |
| NAD+ | Mitochondrial peptide vs coenzyme/redox cofactor | Not characterized vs short | mg subcutaneous vs larger mg, often IV | Different mechanisms within mitochondrial/metabolic biology | Both not approved as drugs |
Featured in these stacks
Retatrutide + MOTS-c
This pairing combines a powerful appetite-and-expenditure agent with a metabolic-conditioning peptide. Retatrutide, the triple-G agonist (GIP/GLP-1/glucagon), drives the weight loss — appetite suppression plus glucagon-mediated energy expenditure. MOTS-c is a mitochondrial-derived peptide encoded within the 12S rRNA gene that activates AMPK and is reported to improve insulin sensitivity, glucose handling, and metabolic flexibility, acting in skeletal muscle as a so-called 'exercise mimetic.'
Sources & references
- [1]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. ↗ source
- [2]Reynolds JC et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun 2021. ↗ source
Frequently asked questions
What does it mean that MOTS-c is 'mitochondrial-derived'?
Most cellular proteins are encoded by the nuclear genome. MOTS-c is unusual because it is encoded within the mitochondrial DNA itself, which is why it is described as a mitochondrial-derived peptide that can signal between the mitochondria and the rest of the cell.
Is the human dosing for MOTS-c established?
No. The mechanistic work is preclinical, and the doses commonly cited (around 5–10 mg, two to three times weekly) come from community protocols rather than controlled human trials. They should be treated as unvalidated.
Related protocols
Humanin
HN
Cytoprotective mitochondrial-derived peptide; preclinical evidence with no human RCTs
NAD+
Nicotinamide adenine dinucleotide
Central redox coenzyme; declines with age (mechanistic interest)
SS-31
Elamipretide
40 mg/day SC; MMPOWER-3 Phase 3 missed its 6-minute-walk primary endpoint
Looking to match this protocol to a verified research vial? Our partner supplier publishes a certificate of analysis per batch.
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.