What is MOTS-C?
MOTS-C is a small peptide encoded not in the cell’s main genome but in the DNA of its mitochondria. Here is how it was discovered, what it does to metabolism, and how it links to exercise and ageing.
At a glance
A peptide from the mitochondrial genome
Mitochondria, the cell's energy-producing structures, carry their own small genome, separate from the DNA in the nucleus. In 2015, researchers reported that a short stretch of mitochondrial DNA inside the gene for the 12S ribosomal RNA also codes for a 16-amino-acid peptide. They named it MOTS-c, for mitochondrial open reading frame of the twelve S rRNA-c.1 It belongs to a small family of mitochondrial-derived peptides, signalling molecules that let mitochondria communicate with the rest of the cell and body.
How it acts on metabolism
The discovery study found that MOTS-c acts mainly on skeletal muscle. Inside cells it slows the folate cycle and the purine production linked to it, which activates AMPK, the cell's main energy sensor. In mice, MOTS-c treatment prevented both age-related and high-fat-diet-induced insulin resistance, as well as diet-induced obesity.1
A message from mitochondria to the nucleus
A 2018 study showed that under metabolic stress, such as glucose restriction, MOTS-c moves into the nucleus, a step that depends on AMPK. There it regulates genes involved in the stress response, including genes with antioxidant response elements, and interacts with stress-responsive transcription factors such as NRF2.2 The finding suggests the mitochondrial and nuclear genomes encode factors that regulate each other.2
Exercise and ageing
MOTS-c has also been linked to exercise. In a 2021 study, a single session of stationary cycling raised MOTS-c gene activity in the thigh muscle of young men about 12-fold and circulating MOTS-c about 1.6-fold. In mice, MOTS-c treatment improved physical capacity and healthspan in older animals, leading the authors to describe it as an exercise-induced regulator of age-related physical decline.3
MOTS-C is not an approved medicine. The treatment effects above come from mouse studies; the human data are measurements of the body’s own MOTS-c.
Where MOTS-C is used in the lab
Laboratory research on MOTS-C centres on AMPK signalling, glucose uptake and insulin sensitivity, exercise-related metabolic adaptation and mitochondrial biology. It is often studied alongside NAD+ and the mitochondria-targeted peptide SS-31, and in metabolic models next to incretin-based compounds such as GLP-3RT.
Handling MOTS-C in the lab
Lyophilized MOTS-C is stable stored frozen at −4 °F and protected from light. Let a vial reach room temperature before opening, reconstitute with bacteriostatic water added slowly down the side of the vial, swirl rather than shake, and keep the solution refrigerated at 36–46 °F.
Before using any lot, check its certificate of analysis. Our current MOTS-C lot, VD-MOTS10-2610, tested at 99.50% purity by HPLC with identity confirmed by LC-MS at VeriPure Labs (10mg vial tested). View the certificate ↗ or see every lot on our lab reports page.
Frequently asked questions
What does MOTS-c stand for?
Mitochondrial open reading frame of the twelve S rRNA-c. It is encoded within the mitochondrial gene for 12S ribosomal RNA.
Where is MOTS-c made?
It is encoded in mitochondrial DNA rather than the nuclear genome, which makes it one of a small family of mitochondrial-derived peptides.
How is MOTS-c linked to exercise?
In a 2021 study, a single cycling session raised MOTS-c gene activity in human muscle about 12-fold and circulating MOTS-c about 1.6-fold.
Is MOTS-C for human use?
No. Vivid DNA supplies MOTS-C strictly for laboratory research. It is not a drug, food or supplement, and is not for human or veterinary use.
References
- Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. 2015;21(3):443–454. PubMed 25738459 ↗
- 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 Metabolism. 2018;28(3):516–524. PubMed 29983246 ↗
- Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021;12:470. doi:10.1038/s41467-020-20790-0 ↗
More research overviews
Research use only. Vivid DNA products are sold strictly for laboratory research. They are not drugs, foods, cosmetics or supplements, are not for human or veterinary use, and are not intended to diagnose, treat, cure or prevent any disease. Clinical results described here refer to investigational or approved medicines studied under medical supervision, not to research-grade material. This article summarises published research and has not been evaluated by the Food and Drug Administration.