MOTS-c

MOTS C 40MG provides MOTS-c as lyophilized powder in a 5 mL vial.

MOTS-c: a peptide encoded in mitochondrial DNA

MOTS-c is a 16-amino-acid mitochondrial derived peptide (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg). Its name stands for mitochondrial open reading frame of the 12S rRNA type-c, because the sequence is written in mitochondrial DNA rather than nuclear DNA. Lee et al. first described it in 2015 [1]. This vial holds 40 mg as a lyophilized powder. If you shop MOTS-c by size, MOTS C 10MG and MOTS C 20MG are smaller options from the same catalog.

MOTS-c belongs to a small group of mitochondrial peptides that act as signaling molecules beyond the mitochondria, a form of mitochondrial signaling to the rest of the cell. That makes MOTS-c research one of the more active areas in metabolic regulation.

How MOTS-c works at the cellular level

At the cellular level, MOTS-c operates through the methionine-folate cycle. In cell studies it raised levels of AICAR, an intermediate that switches on AMP activated protein kinase (AMPK), the enzyme that senses low cellular energy [1]. AMPK activation pushes cells toward glucose uptake and fat oxidation. Under metabolic stress, Kim et al. (2018) found that MOTS-c moves from the cytoplasm into the nucleus and binds to promoters of stress-response and antioxidant genes [2]. That nuclear step is how it helps cells adapt to glucose and caloric restriction and oxidative stress. Researchers are still working out how MOTS-c works in whole tissues.

Energy metabolism and cellular energy production

Because AMPK pathways sit at the center of energy homeostasis, MOTS-c is studied as a regulator of energy metabolism, cellular energy production and mitochondrial function. In mouse models, MOTS-c activates AMPK in skeletal muscle and shifts metabolism toward glucose utilization [1]. Researchers also study it in mitochondrial dysfunction and mitochondrial biogenesis, though direct data on mitochondrial health in people are lacking.

Insulin sensitivity and glucose regulation in animal models

In the 2015 study, MOTS-c treatment prevented diet induced obesity in mice on a high-fat diet and reversed age-dependent insulin resistance in skeletal muscle [1]. Kim et al. (2019) found that MOTS-c changed plasma metabolites in mice and enhanced insulin sensitivity, a step toward understanding its role in glucose regulation [3]. Whether it can improve insulin sensitivity in people hasn’t been tested. These data are why MOTS-c is studied in blood sugar regulation, metabolic syndrome and other metabolic disorders, alongside other metabolic peptides.

Fat metabolism and metabolic health

Lu et al. (2019) studied mice whose ovaries had been removed, a model of estrogen loss. MOTS-c increased brown fat activity, reduced fat build-up and limited adipose inflammation [4]. Across studies, the picture is increased fat oxidation, better metabolic flexibility and metabolic efficiency, and metabolic homeostasis under a high-fat diet. These findings tie MOTS-c to fat metabolism and make it a promising tool for studying metabolic health and metabolic adaptation in animal models. It isn’t evidence for treating obesity in people.

Healthy aging and exercise capacity research in mice

Circulating MOTS-c levels rise after exercise. In older mice, Reynolds et al. (2021) linked MOTS-c to muscle function, muscle health markers and age-dependent physical decline [5]. MOTS-c levels also fall with age, which ties it to age related decline and cellular aging research. A MOTS-c variant (m.1382A>C, K14Q) found in Japanese populations has been studied for links to exceptional longevity [6]. These are mouse and population findings, not evidence that MOTS-c supplementation does anything in humans.

Cellular stress and cellular survival

Under cellular stress, nuclear MOTS-c switches on antioxidant response genes [2]. In cell studies this supports cellular survival and cellular resilience during nutrient restriction. Whether these effects matter in human tissue is still preliminary research.

Regulatory status and what is unknown

MOTS-c is not FDA approved for any use, and there are no human clinical trials of MOTS-c administration. It isn’t a peptide therapy, and there is no approved MOTS-c therapy. Claims that frame it as anti aging medicine or one of the metabolic therapies go beyond the data. No regulatory bodies have approved it, and it is sold only as a research compound. Long-term effects and possible unintended consequences of raising MOTS-c levels are unknown. Unlike growth hormone secretagogues, it does not act on the pituitary, so findings from that class don’t apply.

Quality testing and storage

Certified Peptides manufactures in a cGMP facility in Texas. Every batch is tested by an ISO/IEC 17025 accredited US lab for purity (HPLC), quantity, identity (LC-MS), endotoxins, heavy metals and sterility. When you buy MOTS-c peptide online from us, each vial carries a QR-coded lot number that links to its report in the COA Library. Keep vials sealed, cold and away from light, and see Lab Testing for the full panel.

Related research compounds include MITO BLEND 120MG, which contains MOTS-c, and NAD+.

Questions researchers ask

Where in the mitochondrial genome is MOTS-c encoded?

MOTS-c comes from a short open reading frame inside MT-RNR1, the gene for the mitochondrial 12S ribosomal RNA [1]. Most known signaling peptides are encoded in nuclear DNA, so MOTS-c belongs to a small group of mitochondrial-derived peptides. Along with humanin, it showed that the mitochondrial genome encodes more than the 13 proteins previously known.

How does MOTS-c activate AMPK?

In cell studies, MOTS-c slowed the folate cycle and the de novo purine synthesis that depends on it [1]. That caused AICAR, a purine intermediate, to build up, and AICAR switches on AMPK. AMPK activation is upstream of most of the metabolic effects reported in mice.

What happens to MOTS-c under metabolic stress?

Under glucose restriction or oxidative stress, MOTS-c moves from the cytoplasm into the nucleus in an AMPK-dependent way [2]. There it binds to gene promoters alongside the transcription factor NRF2 and shifts the expression of antioxidant and stress-response genes. That nuclear role helps explain how a mitochondrial peptide influences nuclear gene programs.

How is MOTS-c different from humanin?

Both are mitochondrial-derived peptides, but they come from different genes and are studied for different things. Humanin is 24 residues, encoded in the 16S rRNA region, and studied mainly for cell survival and neuroprotection. MOTS-c is 16 residues from the 12S rRNA region and is studied mainly for metabolism through AMPK [7].

Has MOTS-c been tested in humans?

Native MOTS-c has not. CB4211, a modified analog developed by CohBar, went through a phase 1a/1b program reported in 2021: a dose-ranging study in 65 healthy adults, then a 4-week study in 20 adults with fatty liver [8]. Those data come from a different molecule and don’t describe this peptide.

Why does MOTS-c need careful handling?

The sequence contains two methionines and a tryptophan, residues that oxidize easily. Each methionine oxidation adds 16 Da, so oxidized material shows up as a mass shift on LC-MS. Keep vials sealed, cold and dark, limit air exposure once open, and confirm the 2,174.6 g/mol identity on the lot COA.

Disclaimer

For laboratory research use only. Not for human or veterinary use. Not for consumption. This product is not a drug, food or cosmetic. Information on this page is for educational purposes, has not been evaluated by the FDA, and is not intended to diagnose, treat, cure or prevent any disease.

References

1. Lee C et al. “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” Cell Metab. 2015;21(3):443-454. PubMed
2. Kim KH, Son JM, Benayoun BA, Lee C. “The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.” Cell Metab. 2018;28(3):516-524.e7. PubMed
3. Kim S-J et al. “The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity.” Physiol Rep. 2019;7(13):e14171. PubMed
4. Lu H et al. “MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction.” J Mol Med. 2019;97(4):473-485. PubMed
5. Reynolds JC et al. “MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.” Nat Commun. 2021;12:470. PubMed
6. Fuku N et al. “The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity?” Aging Cell. 2015;14(6):921-923. PubMed
7. Lee C, Kim KH, Cohen P. “MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism.” Free Radic Biol Med. 2016;100:182-187. PubMed