MOTS-c
Mitochondrial-derived signaling peptide encoded in the mitochondrial genome. Activates AMPK and regulates metabolic homeostasis. Under active clinical investigation with a 2026 Phase 2a trial underway.
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA type-c) is a 16-amino acid peptide encoded within the mitochondrial genome — specifically within the 12S rRNA sequence. This unique mitochondrial origin is significant: MOTS-c represents a class of mitochondria-derived peptides (MDPs) that act as retrograde signals from mitochondria to the nucleus to regulate metabolic stress responses.
The primary mechanism involves AMPK (AMP-activated protein kinase) activation. AMPK is a master metabolic regulator that promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and autophagy while inhibiting anabolic energy-consuming pathways. This profile positions MOTS-c as an “exercise mimetic” in research contexts.
A 2026 Phase 2a clinical trial for MOTS-c is underway, though the specific dose is not publicly disclosed in the registry. Physician practice use (1–2 mg daily per Joseph) is ahead of the formal clinical evidence base, extrapolating from extensive preclinical data.
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MOTS-c is not approved for any indication. Research use only. Human safety data is limited — physician practice experience without formal systematic adverse event reporting. The Phase 2a trial will provide the most rigorous human safety data to date. Not currently WADA-prohibited (verify current list). All information for educational reference only.