For laboratory research use only. Not for human consumption.

Metabolic SeriesMitochondrial Research

MOTS-C

Mitochondrial Open Reading Frame of the 12S rRNA Type-C

MOTS-C is a 16-amino acid peptide encoded by the mitochondrial genome — discovered in 2015, it represents a novel class of signaling molecules called mitochondrial-derived peptides. Before MOTS-C, mitochondria were understood primarily as energy-producing organelles. Its discovery demonstrated that mitochondria also produce peptide hormones that regulate metabolic homeostasis at a systemic level, fundamentally expanding how researchers think about organelle function and intercellular communication.

Why Researchers Study It

MOTS-C went from an unknown reading frame in mitochondrial DNA to a well-characterized signaling peptide in less than a decade. The finding that it is exercise-induced, that its levels decline with age, and that it translocates to the nucleus during metabolic stress gives researchers a uniquely rich compound for studying the intersection of metabolism, exercise physiology, and aging.

Metabolic Regulation

Published research has documented MOTS-C's ability to target skeletal muscle and enhance glucose metabolism through the Folate-AICAR-AMPK pathway.

Exercise Physiology

A Nature Communications study demonstrated that MOTS-C is exercise-induced and enhanced physical performance in mice across all age groups.

Aging & Healthspan Research

Studies have documented that circulating MOTS-C levels decline with age in humans, and late-life treatment improved healthspan markers in preclinical models.

Mito-Nuclear Communication

Researchers demonstrated that MOTS-C translocates from mitochondria to the nucleus during stress, regulating genes with antioxidant response elements — a novel signaling pathway.

Research Timeline

8 milestones spanning 2015–2025

Key Milestones
  • Discovered as the first metabolic mitochondrial-derived peptide in Cell Metabolism (2015)
  • Exercise-induced regulation and healthspan improvement published in Nature Communications (2021)
  • Nuclear translocation during metabolic stress revealed a novel mito-nuclear pathway (2019)

Published Research

Selected citations from the published literature.

Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline. Nat Commun. 2021;12:470.

PMID: 33473105

Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis. Cell Metab. 2015;21(3):443-454.

PMID: 25738459

Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging.

PMID: PMC9854231

Research Use Compliance

All information presented on this page references published preclinical research and is provided for educational and informational purposes only. These products are intended for laboratory research use only. Not for human consumption. No statements on this page have been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.