What it is
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial genome. Identified in 2015 by Lee et al. as the first known mitochondria-derived peptide with a clear signalling function outside the organelle.
Evidence snapshot
Category: Mitochondrial. Status: Preclinical. See the references section below for the underlying primary sources.
Mechanism
MOTS-c activates AMPK — the central cellular energy sensor — and intersects with the folate cycle. Under stress, MOTS-c translocates to the nucleus and modulates expression of nuclear-encoded genes.
Key research findings
Across rodent models, MOTS-c has been reported to improve insulin sensitivity on obesogenic diets, prevent diet-induced obesity, improve bone density in osteoporosis models, modulate inflammation.
Limits of the evidence
No large human RCTs. The ‘exercise-mimetic’ framing is premature. Endogenous MOTS-c is a real biomarker but exogenous MOTS-c as a therapeutic is a hypothesis.