MOTS-c: The Peptide Written in Mitochondrial DNA

For laboratory research use only. Not for human or veterinary use.

Almost every peptide in a research catalogue is coded for by the DNA in the cell nucleus. MOTS-c is not. It is written in the mitochondria’s own small genome, inside a gene that was thought for decades to code only for part of the mitochondrial ribosome. It was described in 2015, which makes it one of the newest compounds anyone sells. This guide sets out what MOTS-c is, where it came from, what has been found in mice and in people, who stands behind the research, and what to check on a certificate.

Identity#

The masses are our own calculation from the sequence. Two features matter later: two methionines (positions 1 and 6), which oxidise easily, and five strongly basic residues (four arginines and a lysine), which carry counter-ions.

Where it came from#

Mitochondria carry their own DNA, a small circle of about 16,500 base pairs, inherited from the mother. Its 37 genes were long thought to be fully mapped. Then in 2001 a short peptide called humanin was found to be encoded inside one of them, and researchers began looking for more short reading frames hidden in the mitochondrial genome.

In 2015, Changhan Lee, Pinchas Cohen and colleagues at the University of Southern California reported one inside the gene for the 12S ribosomal RNA. It coded for a 16-residue peptide, which they named MOTS-c. Its main target appeared to be skeletal muscle.

What the animal research found#

• 2015: the mechanism. In cells, MOTS-c held back the folate cycle and the purine synthesis tied to it, which led to activation of AMPK, the cell’s energy sensor. That is the same enzyme our AICAR guide covers. In mice, MOTS-c prevented the drop in insulin sensitivity that came with age and with a high-fat diet, and prevented diet-driven weight gain.
• 2018: into the nucleus. Under metabolic stress such as glucose restriction, MOTS-c moved from the cytoplasm into the cell nucleus, in a way that depended on AMPK. There it affected a broad range of nuclear genes, including antioxidant-response genes, and interacted with the transcription factor NRF2. The authors presented it as the first evidence of a factor encoded in mitochondrial DNA actively controlling the nuclear genome.
• 2021: physical capacity. In young, middle-aged and old mice, MOTS-c raised physical capacity. Treatment started late in life, at about 23.5 months, three times a week, increased physical capacity in old mice.
• 2024: a direct target. MOTS-c bound and activated the enzyme CK2 in muscle, while suppressing it in fat. Blocking CK2 blunted MOTS-c’s effects on muscle in mice.
• 2026: an independent laboratory. A Copenhagen group, unconnected to the original team, reported that MOTS-c improved how efficiently mouse muscle mitochondria produce energy, depending on both PGC-1α and AMPK.

The animal picture is consistent and growing. It is still an animal picture.

What has been found in people#

We have found no published controlled trial of MOTS-c given to people. The human research so far measures the body’s own MOTS-c rather than testing the peptide.

• Exercise. The 2021 paper reported that exercise raised MOTS-c in human muscle and blood. A separate study the same year randomised 30 people to endurance exercise, resistance exercise or rest. Circulating MOTS-c showed only a trend to rise after endurance exercise, and resting levels were not related to fitness.
• A natural variant. Some people in Northeast Asia carry a mitochondrial DNA change, m.1382A>C, that swaps residue 14 of MOTS-c from lysine to glutamine (K14Q). A 2015 paper suggested it might play a part in Japanese longevity. A 2021 analysis of three cohorts, 27,527 people in all, found the opposite direction for blood-sugar regulation: men carrying the variant had higher rates of a common blood-sugar disorder, particularly those who were least active. In mice, the K14Q version lacked the effects of normal MOTS-c, and in 2024 it was shown not to bind or activate CK2.

MOTS-c is not a licensed medicine anywhere.

Who stands behind the research#

Most MOTS-c research so far comes from the group that discovered it and its collaborators. Their papers disclose a commercial interest: the University of California licensed the MOTS-c intellectual property to a company, CohBar, and senior authors have been consultants to it and shareholders in it. That is declared openly, and it does not make the findings wrong. It is a reason to give independent replication, like the 2026 Copenhagen work, extra weight as it appears.

What to check on the certificate#

• Mass: 2174.59 (monoisotopic 2173.11). A peptide this size appears on a mass spectrum as several charged ions: expect peaks near 1087.6 (doubly charged), 725.4 (triply) and 544.3 (quadruply).
• Methionine oxidation. Each oxidised methionine adds 16. Peaks near 2190.6 or 2206.6 mean one or both methionines have oxidised.
• Net peptide content and counter-ion. With five basic residues plus the free amino end, MOTS-c can carry up to six counter-ions. As a trifluoroacetate salt, that can be roughly a quarter of the weight in the vial. Net peptide content tells you how much of the powder is actually MOTS-c, and it can differ a lot from the purity figure.
• Purity, with the method named, measured on that batch.

Ask about the documentation for the batch we would ship before you order. See also how to read a COA, how much is actually in the vial and what a purity figure means.

Handling and storage#

Standard peptide handling applies, with extra care over air because of the two methionines. Store the sealed lyophilised vial cold, dry and in the dark, and let it reach room temperature before opening so moisture does not condense inside. Reconstitute by running bacteriostatic or sterile water down the vial wall rather than onto the powder, and swirl rather than shake. Once in solution, keep it refrigerated and avoid repeated freezing and thawing. The reconstitution guide, solvent guide and storage guide cover the detail.

What Pioneer supplies#

MOTS-c is stocked in 20mg and 40mg vials, with a 10mg vial made to order in one to two weeks.

Quality comes first#

MOTS-c is a 16-residue peptide with two methionines that oxidise and five basic residues that carry counter-ion weight, so both the identity and the amount of peptide in a vial need checking. Ask about the documentation for the batch we would ship before you order.

Sources#

Each entry links to its PubMed record, where the title and abstract can be read. The descriptions are ours: they say what each paper examined, not what it is claimed to show. Records checked on PubMed on 30 October 2026.

1. Lee C, Zeng J, Drew BG, et al. (2015). Cell Metab 21(3):443–54. The first description of MOTS-c: where it is encoded, its action on the folate cycle and AMPK, and studies in mice with age and on a high-fat diet. PubMed 25738459
2. Kim KH, Son JM, Benayoun BA, et al. (2018). Cell Metab 28(3):516–524.e7. Movement of MOTS-c into the cell nucleus under metabolic stress, and the nuclear genes it affected there. PubMed 29983246
3. Reynolds JC, Lai RW, Woodhead JST, et al. (2021). Nat Commun 12(1):470. Physical capacity in young, middle-aged and old mice given MOTS-c, and MOTS-c levels in human muscle and blood after exercise. PubMed 33473109
4. von Walden F, Fernandez-Gonzalo R, Norrbom J, et al. (2021). J Appl Physiol 131(3):1035–42. 30 people randomised to endurance exercise, resistance exercise or rest, measuring circulating MOTS-c and humanin. MOTS-c showed only a trend to rise. PubMed 34351816
5. Fuku N, Pareja-Galeano H, Zempo H, et al. (2015). Aging Cell 14(6):921–3. Short report on the m.1382A>C variant in the MOTS-c sequence, specific to Northeast Asian populations, in the context of Japanese longevity. PubMed 26289118
6. Zempo H, Kim SJ, Fuku N, et al. (2021). Aging (Albany NY) 13(2):1692–1717. Meta-analysis of three cohorts (27,527 people) on the m.1382A>C variant, which changes residue 14 of MOTS-c, with mouse and cell experiments on the variant peptide. PubMed 33468709
7. Kumagai H, Kim SJ, Miller B, et al. (2024). iScience 27(11):111212. Identification of the enzyme CK2 as a direct target of MOTS-c in muscle and fat, including the variant peptide’s reduced binding. PubMed 39559755
8. Gudiksen A, Hansen CC, van der Stede T, et al. (2026). Free Radic Biol Med 246:682–96. Independent laboratory study of MOTS-c and muscle mitochondrial function in two transgenic mouse strains, testing the roles of PGC-1α and AMPK. PubMed 41520850

In our catalogue#

• MOTS-c — 20mg and 40mg in stock; 10mg made to order

Pioneer Research Peptides — UK supplier of research peptides for laboratory use. Ask about batch documentation before you order.

For laboratory research use only — not for human consumption. 18+.