Research Reference · Mitochondrial & Metabolic Research
MOTS-c
A 16-amino-acid peptide encoded in mitochondrial DNA, studied as an exercise mimetic in obesity and weight-management, insulin-sensitivity and aging research.
At a glance
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA — one of a small group of “mitochondrial-derived peptides” discovered in the last decade. Exercise raises its levels in muscle and blood, and in mice it improved insulin sensitivity and physical capacity, which is why it is studied as an “exercise mimetic” in metabolic and aging research. The evidence is preclinical.
What it’s studied for
Insulin sensitivity & obesity
In mice it prevented diet-induced obesity and age- and diet-related insulin resistance. 1
AnimalExercise & physical capacity
Late-life treatment increased physical capacity in mice; in people, exercise raises natural MOTS-c. 2
Animal · human observationMOTS-c
MOTS-c (10mg) · $44.99
Third-party tested · batch-matched COA · research use only
How it works
MOTS-c is unusual because it is coded in the small genome inside mitochondria rather than in the cell nucleus. Its main target appears to be skeletal muscle, where it inhibits the folate cycle and linked purine synthesis, activating AMPK — the cell’s energy sensor. 1
Under metabolic stress, MOTS-c moves from the cytoplasm into the nucleus and regulates a broad set of genes, including antioxidant-response genes, working with the stress-responsive transcription factor NRF2. 3 Researchers see this as evidence that the mitochondrial and nuclear genomes communicate through peptides they encode. 7
In people, exercise increases MOTS-c in skeletal muscle and in circulation, and in mice treatment started late in life increased physical capacity. 2
Related research
Frequently asked questions
What does MOTS-c stand for?
Why is MOTS-c called an “exercise mimetic”?
Has MOTS-c been studied in humans?
How is MOTS-c different from most peptides?
What is the CAS number of MOTS-c?
Identifiers
| Name | MOTS-c |
|---|---|
| Full name | Mitochondrial open reading frame of the 12S rRNA type-c |
| Class | Mitochondrial-derived peptide (16 amino acids) |
| Sequence |
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg |
| Molecular formula | C101H152N28O22S2 |
| Molecular weight | 2174.6 g/mol |
| CAS number | 1627580-64-6 |
| PubChem CID · UNII | 146675088 · A5CV6JFB78 |
| Supplied as | Lyophilized (freeze-dried) powder |
Identifiers checked against PubChem (CID 146675088).
Research timeline
- 2015MOTS-c identified: promotes metabolic homeostasis and reduces obesity and insulin resistance in mice. 1
- 2018MOTS-c shown to enter the nucleus under metabolic stress and regulate gene expression. 3
- 2019Review: a mitochondrial-encoded regulator of the nucleus. 7
- 2021Exercise-induced MOTS-c and late-life physical capacity in mice. 2
- 2023Reviews of MOTS-c in stress, metabolism and aging. 4,5
- 2024Review of mitochondrial-derived peptides in cardiovascular disease. 6
Key studies
| Study | Model | What it found |
|---|---|---|
| Lee 2015 1 | Mouse + cell | Prevented age- and diet-related insulin resistance and diet-induced obesity; activates AMPK. |
| Kim 2018 3 | Cell | Moves to the nucleus under glucose restriction; regulates antioxidant-response genes with NRF2. |
| Reynolds 2021 2 | Mouse + human | Late-life treatment increased physical capacity; exercise raises MOTS-c in human muscle and blood. |
| Wan 2023 4 | Review | Retrograde signaling to the nucleus, energy metabolism, stress homeostasis and aging. |
Sources
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Lee C, et al. Cell Metab, 2015. Free full text
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds JC, et al. Nat Commun, 2021. Free full text
- The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Kim KH, et al. Cell Metab, 2018. Free full text
- Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. Wan W, et al. J Transl Med, 2023. Free full textReview
- MOTS-c Functionally Prevents Metabolic Disorders. Gao Y, et al. Metabolites, 2023. Free full textReview
- Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities. Li Y, et al. J Adv Res, 2024. Free full textReview
- MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus. Benayoun BA, Lee C. Bioessays, 2019. Free full textReview
Last reviewed September 2026 by Midwest Compounds. Every source above was checked against its original publication.