MOTS-c: A Mitochondrial-Derived Peptide in Metabolic Research
A peptide encoded in the mitochondrial genome, and what published work says about its role in metabolism and stress response.
MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino-acid peptide, MRWQEMGYIFYPRKLR, encoded within the mitochondrial genome rather than the nuclear genome. It belongs to a small class of mitochondrial-derived peptides, alongside humanin and the SHLP family, that act as signalling molecules between mitochondria and the rest of the cell. It was first described in 2015 by Changhan David Lee and colleagues at the University of Southern California.
Mechanism overview
In published work, MOTS-c acts on cellular metabolism chiefly through the folate-methionine cycle and activation of AMP-activated protein kinase (AMPK), the cell's energy-sensing kinase. Under metabolic stress, MOTS-c has also been reported to move into the nucleus and influence adaptive stress-response gene expression.
Published research applications
Rodent studies have examined MOTS-c in diet-induced obesity and insulin resistance, skeletal-muscle metabolism, and exercise physiology. Circulating MOTS-c levels were reported to rise with exercise in both humans and mice, and ageing-model studies have asked whether MOTS-c treatment changes physical performance in older animals.
A naturally occurring variant, K14Q, has been associated with differences in metabolic traits in some human cohorts, which makes the peptide a subject of population-genetics research as well as bench work.
Limits of the evidence
MOTS-c research is recent, the first paper is barely a decade old, and most of the evidence is preclinical. Results from rodent models should not be assumed to carry over to other systems.
Reconstitution and handling
QSC supplies MOTS-c as lyophilized powder in 10-vial packs of 10 mg, 15 mg, 20 mg, and 40 mg vials. Reconstitute in sterile or bacteriostatic water per your protocol and refrigerate. Aliquot after reconstitution and avoid repeated freeze-thaw cycles; hold long-term stock as lyophilized powder at -20°C.
