MOTS-c
16 amino acid peptide encoded within the mitochondrial genome.
Also known as: Mitochondrial open reading frame of the twelve S rRNA-c
MOTS-c is one of a small family of peptides encoded within mitochondrial DNA rather than nuclear DNA. It was identified in 2015 by researchers at the University of Southern California and has since become a focus of research into mitochondrial communication, metabolism, and aging biology.
Key facts
- Structure
- 16 amino acid peptide
- Origin
- Encoded within the 12S ribosomal RNA region of mitochondrial DNA
- Discovery
- Identified and characterized in 2015 by Changhan Lee and colleagues
- Primary research focus
- Metabolism, insulin sensitivity, exercise adaptation, aging biology
- Regulatory status
- Not approved for any therapeutic use
What is MOTS-c?
MOTS-c stands for Mitochondrial Open reading frame of the Twelve S rRNA-c. It is a small peptide encoded within a region of the mitochondrial 12S ribosomal RNA gene. Until the discovery of peptides like MOTS-c and humanin, mitochondrial DNA was thought to encode only a handful of proteins involved in the electron transport chain.
The peptide was characterized by Changhan Lee, Pinchas Cohen, and colleagues at the University of Southern California in a 2015 paper published in Cell Metabolism. Research since then has explored its biological roles and potential therapeutic relevance.
Mechanism of action
Published research describes MOTS-c as acting on the AMP-activated protein kinase (AMPK) pathway, a central regulator of cellular energy balance. It has also been reported to translocate to the nucleus under stress conditions and influence gene expression, which would be unusual for a peptide of its size and origin.
- •Acts on the AMPK signaling pathway, a central energy sensor
- •Reported effects on glucose uptake and metabolic adaptation in cell and animal studies
- •May translocate to the nucleus under stress conditions and influence transcription
- •Circulating levels have been reported to decline with age in some human studies
Research context
Preclinical studies in mice have reported that MOTS-c administration produces effects on insulin sensitivity, body composition on high-fat diets, and exercise capacity. These effects have been interpreted as consistent with MOTS-c acting as a mitochondrial-derived signaling molecule that coordinates metabolic adaptation.
Human research on MOTS-c is more limited. Observational studies have reported correlations between circulating MOTS-c levels and age, exercise status, and certain disease states. Interventional human trials of exogenous MOTS-c administration are scarce, and no large phase 2 or phase 3 trials have been published.
Safety and regulatory context
MOTS-c is not approved by the FDA or any regulatory agency for any therapeutic indication. Published safety data from human administration are minimal, and the overall clinical evidence base is still in early stages.
Material sold as research MOTS-c is intended strictly for laboratory use and is not cleared for human administration. Identity and purity cannot be verified without independent analytical testing.
Research sourcing
MOTS-c is listed by our research partner, GLP1 Research Lab, which supplies lyophilized peptides for laboratory use. Listings include product identifiers relevant to research documentation.
View MOTS-c listing at GLP1 Research LabAffiliate partnership. Metabolic Playbook may earn a commission on purchases made through this link at no additional cost to the researcher.