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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
Last updated · 2026-04-12

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 1627580-64-6
Route Subcutaneous · Intraperitoneal subcutaneous preferred
Where to buy MOTS-c →BioLongevity Labs · save 15% code VIALBASE
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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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Mechanism

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

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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 (meta-analysis of three cohorts) + mouse and in vitro experiments 2021 The Asian-specific mtDNA variant m.1382A>C (rs111033358) causes a K14Q amino-acid replacement in MOTS-c
MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis Animal study (Wistar rat) 2026 In adult male Wistar rats (n = 16), a 24-hour subcutaneous MOTS-c infusion did not alter classical steroidogenic genes or circulating corticosterone and aldosterone
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
Humanin and MOTS-c Attenuate Atrial Fibrillation by Suppressing Fibrosis and Mitochondrial Dysfunction. Translational study (clinical association, animal model, and primary-cell experiments) 2026 Humanin (HN) and MOTS-c were significantly downregulated in human AF atrial tissue, with levels inversely correlated with the extent of fibrosis
MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases. Narrative review 2026 MOTS-c is a mitochondrial-derived microprotein (mitokine) encoded within the 12S rRNA gene that exerts intracrine, paracrine, and endocrine effects across multiple tissues
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis animal study (mouse) + cell experiments + human exercise measurements 2021 MOTS-c significantly enhanced physical performance in young (2 mo), middle-aged (12 mo), and old (22 mo) mice
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. Not on the 503A bulks list and not in any FDA interim category. An FDA advisory committee (PCAC) recommended it for the 503A bulks list on 2026-07-23 — for no evaluated indication; FDA has not adopted that recommendation and compounding MOTS-c is not permitted.
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.

Frequently Asked Questions

What is MOTS-c?
MOTS-c is a longevity compound. Mitochondrial-derived peptide — activates AMPK pathway, regulates folate-methionine cycle, improves metabolic homeostasis, enhances insulin sensitivity, modulates mTOR signaling.
How does MOTS-c work?
MOTS-c operates through a unique mitochondria-to-nucleus signaling pathway: 1. AMPK activation — MOTS-c's primary mechanism is activation of 5'-AMP-activated protein kinase (AMPK), the master metabolic sensor. AMPK activation shifts cellular metabolism toward catabolic pathways: increased glucose uptake, fatty acid oxidation, and mitochondrial biogenesis.
How is MOTS-c dosed?
Commonly cited research protocols use 5000–10000 mcg, 3-5x weekly, cycles of 4-8 weeks. These figures reflect commonly cited research protocols, not medical advice — consult a clinician.
Is MOTS-c FDA-approved?
No. MOTS-c is not FDA-approved, is not on the 503A bulks list, and is not listed in any of FDA's interim Category 1, 2, or 3 lists — so there is no lawful compounding route. On July 23, 2026 an FDA advisory committee (PCAC) voted to recommend adding MOTS-c to the 503A bulks list, over FDA's own reviewers' recommendation against it. The vote is advisory and non-binding; FDA has not adopted it and compounding MOTS-c is not currently permitted. Note that FDA evaluated no indication for MOTS-c at all — the proposed uses (insulin resistance, obesity, osteoporosis, vascular calcification, muscle/fat metabolism, longevity) were nominated, not evaluated, because the nomination lacked sufficient information.
What does the research on MOTS-c show?
200 PubMed publications as of April 2026. Growing rapidly — majority published after 2020. Discovery paper (Lee et al.

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, Kim SJ, Fuku N, et al.. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY) (2021). PMID: 33468709
  3. Blatkiewicz M, Kaminski K, Sobalska-Kwapis M, et al.. MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis. Folia Histochemica et Cytobiologica (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. Liao Y, Xu J, Jiao Y, et al.. Humanin and MOTS-c Attenuate Atrial Fibrillation by Suppressing Fibrosis and Mitochondrial Dysfunction.. Biomedicines (2026). PMID: 42193373
  6. Amado CA, Agüero J, García-Unzueta M, et al.. MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases.. Journal of translational medicine (2026). PMID: 42243958
  7. 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: 33473109
  8. 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: 25738459