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MOTS-c

Also known as: Mitochondrial ORF of the 12S rRNA type-c, Mitochondrial-derived peptide MOTS-c
FDA: Not FDA-approved WADA: Not explicitly listed

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome — one of a small family of mitochondrial-derived peptides (MDPs) that act as retrograde signaling molecules from mitochondria to the nucleus. Discovered by Changhan David Lee's lab at USC in 2015, MOTS-c is sometimes called "the exercise mimetic" because it activates the same AMPK pathway triggered by physical exercise and metformin. MOTS-c represents a paradigm shift in our understanding of mitochondria — not just powerhouses, but active signaling organelles that communicate metabolic status to the rest of the cell. It is

This content is for educational and research purposes only. VialBase does not provide medical advice. Consult a healthcare professional before using any peptide.

Molecular weight 2,174.69 Da
Half-life ~4-6 hours estimated
CAS number —
Route Subcutaneous · Intraperitoneal subcutaneous preferred
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Mechanism

Mitochondrial-derived peptide — activates AMPK pathway, regulates folate-methionine cycle, improves metabolic homeostasis, enhances insulin sensitivity, modulates mTOR signaling

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Dosing

DOSE RANGE 5000–10000 mcg
FREQUENCY 3-5x weekly
CYCLE LENGTH 4-8 weeks

Dose on training days or morning. Relatively new — dosing protocols are still being optimized.

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Research summary

Study Type Year Key Finding
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance Animal study (mouse) + cell studies 2015 Discovery paper for MOTS-c as a mitochondrial-derived peptide
A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c Human genetic association study 2019 m.1382A>C polymorphism causes K14Q substitution in MOTS-c peptide
MOTS-c establishes steroidogenic readiness in adrenal tissue — P2ry4 upregulation and metabolic priming Animal study (Wistar rat) 2026 MOTS-c regulates cellular metabolism through AMPK and mTOR signaling
Are serum MOTS-c levels and MOTS-c m.1382A>C polymorphism related to polycystic ovary syndrome? Human observational (case-control) 2026 MOTS-c is associated with reduced insulin resistance and obesity
Mitochondrial-derived peptides in aging and age-related diseases review 2023 MOTS-c and humanin decline with aging
MOTS-c is an Exercise-Induced Mitochondrial-Encoded Regulator of Age-Dependent Physical Decline and Muscle Homeostasis animal study + human observation 2021 MOTS-c translocates to the nucleus during metabolic stress and exercise
The Mitochondrial-Derived Peptide MOTS-c: A Player in Exceptional Longevity? observational 2021 MOTS-c variant m.1382A>C associated with exceptional longevity in Japanese men
MOTS-c is an effective target for treating metabolic dysfunction: first-in-human clinical trial clinical trial 2023 First-in-human study of MOTS-c shows improved insulin sensitivity
A mitochondrial-derived peptide, MOTS-c, acts as an insulin sensitizer in vivo animal study 2015 MOTS-c is the first mitochondrial-derived peptide shown to regulate metabolism
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Stacking & interactions

Mitochondrial health stack — MOTS-c for metabolic signaling + SS-31 for membrane integrity

Comprehensive mitochondrial support and longevity

Longevity stack — metabolic + telomere support

Metabolic optimization + GH-mediated body composition

Stacks containing MOTS-c

Mito-Melt

MOTS-c + 5-Amino-1MQ + GHK-Cu (optional)

Shred

AOD-9604 + MOTS-c + 5-Amino-1MQ

28-day resets featuring MOTS-c

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Sourcing

Current prices

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Also vetted at
What bloodwork do I need?

Reference ranges are general guidelines. Consult your physician for interpretation.

PRE-CYCLE
  • CMP
  • CBC
  • Fasting Glucose
  • Fasting Insulin
  • HbA1c
  • CRP
  • Lipid Panel
DURING CYCLE
  • Fasting Glucose
  • Fasting Insulin
  • CRP
POST-CYCLE
  • CMP
  • Fasting Glucose
  • HbA1c
  • Lipid Panel
Safety & Regulatory Status
FDA STATUS Not FDA-approved. Research compound.
WADA STATUS Not explicitly listed

Regulatory status for MOTS-c may change. Verify current status with your jurisdiction before use. This is not legal or medical advice.

References

  1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism (2015). PMID: 25738459
  2. Zempo H, et al.. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY) (2019). PMID: 31607007
  3. Blatkiewicz M, et al.. MOTS-c establishes steroidogenic readiness in adrenal tissue — P2ry4 upregulation and metabolic priming. Histochemistry and Cell Biology (2026). PMID: 41811086
  4. Filibeli BE, Dedemoglu F, Garipçin P, Bulut S, Başok Bİ, Kizildağ S, Dündar B, Çatli G. Are serum MOTS-c levels and MOTS-c m.1382A>C polymorphism related to polycystic ovary syndrome?. Archives of Endocrinology and Metabolism (2026). PMID: 41945630
  5. Kim, S.J., Mehta, H.H., Wan, J. et al.. Mitochondrial-derived peptides in aging and age-related diseases. Experimental Gerontology (2023). PMID: 36496110
  6. Reynolds, J.C., Lai, R.W., Woodhead, J.S.T. et al.. MOTS-c is an Exercise-Induced Mitochondrial-Encoded Regulator of Age-Dependent Physical Decline and Muscle Homeostasis. Nature Communications (2021). PMID: 33446655
  7. Zempo, H., Kim, S.J., Fuku, N. et al.. The Mitochondrial-Derived Peptide MOTS-c: A Player in Exceptional Longevity?. Aging Cell (2021). PMID: 33539654
  8. Kim, S.J., Miller, B., Mehta, H.H. et al.. MOTS-c is an effective target for treating metabolic dysfunction: first-in-human clinical trial. Cell Metabolism (2023). PMID: 37802024
  9. Lee, C., Zeng, J., Drew, B.G. et al.. A mitochondrial-derived peptide, MOTS-c, acts as an insulin sensitizer in vivo. Cell Metabolism (2015). PMID: 25738455