Overview
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In plain language
MOTS-c is a small peptide of 16 amino acids whose genetic instructions sit in mitochondria, the energy factories inside cells. It was discovered in 2015.
In mice, it improved how the body handles sugar and boosted exercise capacity, which made it a hot topic in aging and metabolism research. These effects have not been shown in people, and there is no FDA-approved MOTS-c medicine.
For students
MOTS-c (MRWQEMGYIFYPRKLR, about 2,175 Da) was described by Lee and colleagues in Pinchas Cohen's lab in 2015. It is encoded by a short open reading frame within the mitochondrial 12S rRNA gene (MT-RNR1).
In mice, MOTS-c acted mainly on skeletal muscle, activating AMPK through effects on the folate cycle and purine metabolism. It prevented diet-induced insulin resistance and obesity. Under metabolic stress, it was reported to move into the nucleus and regulate genes involved in stress responses.
For researchers and instructors
Human data. Observational studies measure circulating levels and their changes with exercise, age and disease. A drug analogue (CB4211) entered early clinical trials, but MOTS-c itself has no published randomized efficacy data.
Methodology. Assays for mitochondrial-derived peptides vary, and reported plasma levels differ widely between studies.
Regulatory. No FDA-approved product. Since October 2026, licensed 503A pharmacies may compound it under FDA enforcement discretion, which is not approval.
Molecular identity
- Amino acids
- 16
- Molecular weight
- ~2,174.6 Da
- Formula
- Verify chemical form
- Sequence
- MRWQEMGYIFYPRKLR
Sequence map
Hydropathy
Kyte–Doolittle score per residue. Positive values are water-repelling.
Origin and history
MOTS-c was discovered in 2015 by Changhan David Lee, Pinchas Cohen and colleagues at the University of Southern California. It was a surprise: a 16-amino-acid peptide encoded not in the cell’s nucleus but inside the mitochondrial DNA, in a stretch called the 12S rRNA gene. Its name stands for “mitochondrial open reading frame of the 12S rRNA type-c.”
In mice it improved insulin sensitivity and prevented diet-induced obesity, which made it part of a new field of “mitochondrial-derived peptides” alongside humanin. Human data are still very limited.
Key people
- Changhan David LeeFirst author, USC Leonard Davis School of Gerontology
- Pinchas CohenSenior author, USC
Timeline
- 2001
Humanin, the first mitochondrial peptide, is found
- 2015
MOTS-c reported in Cell Metabolism
- 2020s
Early human studies begin
- 2026
FDA allows 503A compounding under enforcement discretion
See every peptide on one history timeline.
Human evidence
Human efficacy and long-term safety evidence remains limited; do not extrapolate animal findings.
Emerging mitochondrial peptide research, predominantly mechanistic and preclinical.
Explore original publications and distinguish preclinical findings from controlled human evidence.
Safety and regulatory status
See every compound on the regulatory tracker.
No FDA-approved therapeutic MOTS-c product.
Product identity, purity, sterility, and endotoxin testing address different risks. This profile is educational and does not provide treatment guidance.
Sources
Hernandez Gener, E. (2026, November 7). MOTS-c: molecular data, research history and evidence. VALREXA Biosciences. https://valrexa.com/peptides/mots-c.html
APA style · Last reviewed November 7, 2026 · Our editorial standardsLast reviewed November 7, 2026. Trial and regulatory status can change; confirm in the linked registries. This profile is educational and is not medical advice, a treatment recommendation, or dosing or sourcing guidance. Report an error · Corrections policy