Entry 0013Rev 1.0Mitochondrial-derived peptide

MOTS-c

MRWQEMGYIFYPRKLR · C101H152N28O22S2

Reviewed

2 Nov 2026

Scientific editor

[Name, PhD]

References

6 sources

MOTS-c is a 16-residue peptide coded not in the cell nucleus but in mitochondrial DNA, inside the gene for a ribosomal RNA. Pinchas Cohen's group at the University of Southern California reported it in 2015.1

The mouse work links it to insulin sensitivity and exercise capacity. In people, the data are measurements of the body's own MOTS-c, which rises with exercise. No trial has given MOTS-c to people and published the result.

Residues

16

Avg mass

2174.6 g/mol

Discovered

2015

WADA class

S4.4.1

01

Identity

MOTS-c is one of a small group of peptides found to be encoded in mitochondrial DNA. Its open reading frame sits inside MT-RNR1, the gene for the 12S ribosomal RNA, which is where its name comes from.1

Value
SequenceMRWQEMGYIFYPRKLR
Encoded byMT-RNR1 (12S rRNA), mitochondrial DNA
FormulaC101H152N28O22S2
Avg mass2174.6 g/mol
Discovered2015, University of Southern California
02

History

  1. Lee and colleagues report MOTS-c and its effects on insulin resistance and diet-induced obesity in mice.1

  2. Review places it among mitochondrial-derived peptides.2

  3. Shown to rise with exercise in people and to improve physical capacity in older mice.3

  4. Measured in breast cancer survivors before and after an exercise programme.4

  5. WADA names it as a prohibited AMPK activator.6

  6. On the agenda of an FDA compounding advisory meeting.5

03

What the studies measured

AreaModelWhat was measuredSource
MetabolismMice on high-fat dietsWeight gain, insulin sensitivity, AMPK activation in muscle[1]
ExerciseOlder mice; human muscle and blood after exercisePhysical capacity in mice; MOTS-c levels in people[3]
ExerciseBreast cancer survivors in an exercise trialBlood MOTS-c before and after training[4]

Note the difference. The human studies measured MOTS-c the body makes. None gave MOTS-c to people.

04

Regulatory and sport status

WhereStatus
UK, EU, USNot approved anywhere. Not a controlled drug in the UK. May not be supplied or promoted for human use.
USListed for discussion at the FDA's compounding advisory committee in July 2026.5
SportProhibited at all times. Named in WADA class S4.4.1 among activators of AMP-activated protein kinase.6
05

Open questions

  1. What it does when given to people. No human dosing study has been published.
  2. How it works. AMPK activation, nuclear signalling and other routes have all been proposed.
  3. Whether falling levels with age are a cause or a marker of metabolic decline.
06

Common questions

What does MOTS-c stand for?

Mitochondrial open reading frame of the 12S rRNA, type c: the place in mitochondrial DNA that codes for it.

Is MOTS-c made by the body?

Yes. It is found in human blood and muscle, and levels rise with exercise.

Has it been tested in people?

Only measured, not given. No trial of MOTS-c given to people has been published.

Is MOTS-c banned in sport?

Yes, by name, under WADA class S4.4.1, at all times.

Why is it on the mitochondrial shelf?

It is coded in mitochondrial DNA, unlike almost every other peptide in the library.

—

See also

NAD+ Entry 0014Mitochondrial ShelfTesamorelin Entry 0004How we test a lot Method
07

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. PMID 25738459
  2. Lee C, Kim KH, Cohen P. MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016;100:182–187. PMID 27216708
  3. Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12:470. doi:10.1038/s41467-020-20790-0
  4. Dieli-Conwright CM, et al. [Aerobic and resistance exercise and circulating MOTS-c in breast cancer survivors]. Sci Rep. 2021;11:16916. PMID 34413391
  5. American Med Spa Association. FDA advisory committee on compounding, 23 July 2026; MOTS-c on the docket. americanmedspa.org
  6. World Anti-Doping Agency. The 2026 Prohibited List. wada-ama.org Class S4.4.1.

Peptidarium Library. MOTS-c (entry 0013), revision 1.0, 2 November 2026. peptidarium.com/library/mots-c

08

Revision history

RevDateChangeBy
1.02 Nov 2026Entry created.[Scientific editor]

Spotted an error or a missing paper? Send a correction. Every change is logged here.