MOTS-c

Most of the body’s proteins are encoded in the DNA of the cell nucleus, but mitochondria, the cell’s energy-producing structures, carry a small genome of their own. In 2015, researchers at the University of Southern California reported a short open reading frame inside the mitochondrial gene for 12S ribosomal RNA that encodes a 16-amino-acid peptide. They named it MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) ^[1].

MOTS-c is therefore a natural signalling molecule, one of a small family of “mitochondrial-derived peptides” that also includes humanin ^[5]. The MOTS-c sold online is a synthetic copy of the natural sequence, made by peptide manufacturers and labelled for research use. Our guide to what research peptides are explains what that label means in practice.

Interest in MOTS-c comes mainly from its links to metabolism, exercise and ageing. It is often discussed alongside another mitochondria-targeted peptide, SS-31, although the two are unrelated: SS-31 is a designed drug that binds a mitochondrial membrane lipid, whereas MOTS-c is a natural peptide that also circulates in the blood.

In the 2015 study, MOTS-c’s main target appeared to be skeletal muscle. Inside cells it inhibited the folate cycle and the linked pathway that makes purines, which led to activation of AMPK, an enzyme that acts as a cellular energy sensor and increases glucose uptake and fat use ^[1]. AMPK activation is also the property that places MOTS-c on the anti-doping list.

A 2018 study from the same group found that under metabolic stress, such as glucose restriction, MOTS-c moves from the cytoplasm into the cell nucleus in an AMPK-dependent way. There it regulated a broad set of nuclear genes, including antioxidant-response genes, and interacted with stress-responsive transcription factors such as NRF2 ^[2]. The authors presented this as evidence that the mitochondrial genome can directly regulate the nuclear genome.

More recent work has proposed other roles. A 2026 study described MOTS-c as a host defence peptide with direct antibacterial activity against E. coli and MRSA in laboratory tests and in a mouse infection model, and reported that it reprogrammed mouse immune cells ^[10]. These findings are from cell and animal experiments.

The founding study reported that MOTS-c injections in mice prevented insulin resistance associated with ageing and with a high-fat diet, and prevented diet-induced obesity ^[1]. The mice in these experiments received 5 mg/kg per day by intraperitoneal injection, for periods from a few days to eight weeks.

Human genetics offers indirect support. A variant found in East Asian populations (m.1382A>C) changes the 14th amino acid of MOTS-c (K14Q). In a meta-analysis of three cohorts totalling 27,527 people, men carrying the variant had a higher prevalence of type 2 diabetes, especially if they were physically inactive. In mice, the normal peptide reduced weight and improved glucose tolerance on a high-fat diet, but the K14Q version did not ^[4]. This is an association study plus animal work, not a treatment trial.

Not every result has been positive. A 2026 study on fat-derived stem cells from people with obesity found that adding MOTS-c activated AMPK but reduced cell proliferation, increased markers of cellular ageing and inflammation, and did not improve the cells’ ability to repair damaged mouse kidneys ^[11]. Reviews of the field describe MOTS-c as a promising research target for diabetes and age-related disease, while noting that the evidence is preclinical ^[5].

A 2021 study in Nature Communications reported that MOTS-c improved physical performance in young, middle-aged and old mice. Mice given daily injections ran longer on a treadmill, and late-life treatment three times a week improved physical capacity and markers of healthspan in old mice ^[3].

The same paper included the main human data on MOTS-c. In 10 sedentary healthy young men who exercised on a stationary bicycle, MOTS-c levels in muscle rose about 11.9-fold after exercise, and levels in blood rose about 1.5-fold during and after exercise before returning to baseline within four hours ^[3]. This shows that the body produces more MOTS-c during exercise; it does not show that injecting it has the same effects as exercise.

The K14Q variant has also been linked to muscle make-up. In 211 healthy Japanese adults, carriers had a higher proportion of fast-twitch muscle fibres, and the variant was more common in sprint and power athletes than in controls ^[9].

No randomised trial of MOTS-c in people has published results as of September 2026. A US company, CohBar, ran a phase 1a/1b study of CB4211, which it describes as an analogue of MOTS-c, in 88 healthy volunteers and people with fatty liver disease ^[8]. In a 2021 press release the company reported that the four-week phase 1b part, in 20 people with obesity and fatty liver disease, met its safety end point with no serious adverse events, and showed reductions in liver enzymes and glucose compared with placebo ^[13]. These results were announced by the company rather than published in a journal, and CB4211 is a modified molecule, not the peptide sold online.

In 2026 a phase 2a trial of MOTS-c itself began: a randomised, placebo-controlled study in an estimated 120 adults with prediabetes and overweight or obesity, using once-daily subcutaneous injections for 12 weeks ^[7]. Until such trials report, human evidence is limited to measurements of natural MOTS-c levels in observational and exercise studies.

Published doses are from mice. The 2015 study used 5 mg/kg per day by intraperitoneal injection ^[1], and the 2021 exercise study used 5 or 15 mg/kg per day, including an intermittent schedule of three times a week at 15 mg/kg in older mice ^[3].

No human dose has been established. The dose in the 2026 phase 2a trial is not stated in its public registration ^[7]. Animal doses should not be converted into human doses, and PepFinder does not recommend any dose. Our peptide calculator explains reconstitution arithmetic only.

There are no published human safety data for injected MOTS-c. A 2026 review of approved and unapproved peptides used in sports medicine, which included MOTS-c, concluded that rigorous human safety data for these unapproved peptides are scarce and that there is potential for serious harm ^[6]. The stem-cell findings above also show that its effects can be context-dependent ^[11].

As with any unlicensed injectable, the identity, quantity, sterility and endotoxin content of a product depend entirely on the manufacturer. Our guide to third-party peptide testing explains what independent testing can and cannot confirm.

MOTS-c is not an approved medicine in the US, UK, EU, Canada, Australia or New Zealand. The US Anti-Doping Agency states that it is not approved by the FDA for use in humans or in compounded medications ^[12]. Its sale as a research chemical is treated differently in each country; see our legal status pages.

MOTS-c is named on the WADA Prohibited List under S4.4.1, activators of AMP-activated protein kinase, and is prohibited at all times, in and out of competition ^[12]. USADA notes that a therapeutic use exemption is highly unlikely because it has no approved therapeutic use ^[12].

MOTS-c is supplied as a freeze-dried powder. As with other research peptides, the usual practice is to keep it cold, dry and away from light, and to refrigerate it after reconstitution. See how to store peptides and bacteriostatic water.

PepFinder does not sell MOTS-c. To compare research suppliers, see compare prices, learn how to read a COA, and see which vendors use third-party tested batches.