MOTS-c is a peptide encoded within the mitochondrial 12S rRNA gene, first described in 2015. What it is, where it comes from and what it has been studied for.
By the MOTS-C Peptide editorial team·Last reviewed ·Sources: editorially approved
Short answer
MOTS-c is a peptide 16 amino acids long, encoded by a short open reading frame inside the mitochondrial gene MT-RNR1 [Lee et al. 2015][UniProt 2026]. It was described in 2015 and has been detected in human blood and skeletal muscle. Most of what is known about its effects comes from cell and mouse experiments.
A peptide from the mitochondrial genome
Nearly every protein in a human cell is encoded in the nucleus. Mitochondria keep a small circular genome of their own, long thought to encode only a handful of respiratory-chain components plus the RNAs needed to translate them.
MOTS-c came out of a search for coding sequences hidden inside those RNA genes. A 51-base open reading frame within the 12S ribosomal RNA gene yielded a 16-residue peptide [Lee et al. 2015]. UniProt now catalogues it as a reviewed entry with evidence at protein level [UniProt 2026], meaning the peptide itself has been detected, not merely predicted from sequence.
What it is made of
The sequence is MRWQEMGYIFYPRKLR, giving a molecular formula of C101H152N28O22S2 and an average molecular weight of 2174.6 g/mol [PubChem]. At 16 residues it is far smaller than a typical protein and larger than the tripeptides often discussed alongside it. Full identity data, including a residue-level view, is on the molecular data page; third-party identity profiles are published by research suppliers.
What research has reported
The 2015 discovery work described a chain of events in cultured cells: inhibition of the folate cycle, a build-up of the purine-synthesis intermediate AICAR, and activation of AMPK, the enzyme cells use to sense low energy [Lee et al. 2015]. In mice, treatment was associated with less diet-induced and age-related insulin resistance.
A 2018 study reported something less expected: under metabolic stress, MOTS-c moved into the nucleus and was linked to stress-response genes [Kim et al. 2018]. That made it an example of signalling in the less-studied direction, from mitochondrion to nucleus. Both findings come from cultured cells.
In people, research has mostly measured the peptide rather than administered it. Circulating levels were reported lower in older men, while muscle expression was higher [D'Souza et al. 2020], and exercise has been associated with higher levels in muscle and blood [Reynolds et al. 2021]. See the studies grouped by pathway for the full set.
How it is encountered outside the laboratory
MOTS-c is sold as a research chemical and marketed online for weight loss, metabolic health and physical performance. None of those uses is approved, and FDA’s literature search found no studies of compounded MOTS-c products used in humans [FDA 2026]. In competitive sport it is prohibited at all times as an example of an AMPK activator [WADA 2026]. The regulatory status page covers both in detail.
Where to go next
This site indexes 253 publications, 184 of them primary research. If you want the claims assessed one by one, start with what the research has and has not shown. If you want the raw record, open the evidence explorer and filter by study model.
Frequently asked questions
What does MOTS-c stand for?
Mitochondrial Open reading frame of the Twelve S rRNA type-c. The name describes where the coding sequence sits: inside MT-RNR1, the mitochondrial gene for 12S ribosomal RNA.
What does MOTS-c do?
In cells and mice it has been reported to inhibit the folate cycle, raise the purine intermediate AICAR and activate AMPK, and to enter the nucleus under metabolic stress. What it does in people has not been established; its direct molecular target is unknown.
Is MOTS-c a hormone?
It is often described as a mitochondrial-derived peptide that acts beyond the mitochondrion, which is why some authors call it a mitokine. It has no identified receptor, so calling it a hormone goes further than the evidence supports.
Where is MOTS-c found in the body?
It has been detected in human plasma and skeletal muscle. One study reported lower circulating levels and higher muscle expression in older men compared with younger men.
What is MOTS-c used for?
There is no approved use. It is sold as a research chemical and is marketed online for metabolic and performance claims that no published human trial supports. It is also prohibited in competitive sport.
References
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 Metab. PubMed 25738459 · doi:10.1016/j.cmet.2015.02.009 · Study record[Animal, tier C]
Kim KH, Son JM, Benayoun BA et al. (2018). The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. PubMed 29983246 · doi:10.1016/j.cmet.2018.06.008 · Study record[Cells, tier D]
D'Souza RF, Woodhead JST, Hedges CP et al. (2020). Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition. Aging (Albany NY). PubMed 32182209 · doi:10.18632/aging.102944 · Study record[Human obs., tier B]
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. Nat Commun. PubMed 33473109 · doi:10.1038/s41467-020-20790-0 · Study record[Animal, tier C]
National Center for Biotechnology Information. PubChem Compound CID 146675088: Mots-c. Source[retrieved 2026-11-11]
U.S. Food and Drug Administration (2026-05-11). FDA Briefing Document: MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate). Source[retrieved 2026-11-11]
World Anti-Doping Agency (2026-01-01). The Prohibited List (S4 Hormone and Metabolic Modulators: activators of AMP-activated protein kinase). Source[retrieved 2026-11-11]