PeptideFederation

Mitochondrial-derived peptide

MOTS-c

Also known as Mitochondrial open reading frame of the 12S rRNA-c

Animal studies

Summary

MOTS-c is a 16-amino-acid peptide encoded by mitochondrial DNA, discovered in 2015. It acts mainly on skeletal muscle, where it improves insulin sensitivity. In mice it prevented diet-induced obesity and, in older animals, improved physical capacity. Blood levels rise with exercise in people.

Structure

  1. M1
  2. R2
  3. W3
  4. Q4
  5. E5
  6. M6
  7. G7
  8. Y8
  9. I9
  10. F10
  11. Y11
  12. P12
  13. R13
  14. K14
  15. L15
  16. R16

HydrophobicGly / ProPolarBasic (+)Acidic (−)

Encoded in the mitochondrial genome, within the 12S ribosomal RNA gene.

How it works

MOTS-c inhibits the folate cycle and de novo purine synthesis, which raises AICAR levels and activates AMPK. Under metabolic stress it moves into the nucleus and regulates genes involved in antioxidant responses.

Research use cases

Areas where MOTS-c has been studied. Inclusion here does not mean it works for that purpose.

  • Insulin resistance and obesity models
  • Age-related decline in physical capacity
  • Exercise physiology

What the research found

Discovery and metabolism

Lee and colleagues showed that MOTS-c targets skeletal muscle, activates AMPK, and prevented both diet-induced obesity and insulin resistance in mice.1

Exercise and ageing

Exercise raised MOTS-c in human skeletal muscle and blood. Treating old mice improved physical performance, and late-life intermittent treatment increased healthspan measures.2

Safety and open questions

No published controlled human trials of MOTS-c itself. An analog (CB4211) entered early clinical testing but has not reported definitive results.

Regulatory status

Not approved. Included in the July 2026 FDA advisory committee compounding vote. Sold for research use.

Status was accurate when this page was last reviewed on October 26, 2026. Regulations change; check with the relevant authority before relying on it.

MOTS-c: common questions

Is MOTS-c a hormone?

It behaves like one in some respects: it is made in cells, circulates in blood and acts on distant tissues. Researchers describe it as a mitochondrial-encoded signalling peptide, or mitokine.

Is MOTS-c approved for human use?

Not approved. Included in the July 2026 FDA advisory committee compounding vote. Sold for research use.

References

  1. Lee C, Zeng J, Drew BG, et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism.
  2. Reynolds JC, Lai RW, Woodhead JST, et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications.

Links open a PubMed search for the exact title, or the original source where one is given.