MOTS-c — The Mitochondrial-Derived Peptide

Background

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene, identified by Lee and colleagues at USC in 2015. It is one of the first peptides shown to be encoded by mitochondrial DNA itself.

Mechanism

MOTS-c translocates to the nucleus under metabolic stress and modulates nuclear gene expression involved in metabolic adaptation. Documented effects in published work include AMPK pathway activation, enhanced glucose disposal, and protection against age-related insulin resistance.

What is proven

In rodents, MOTS-c administration prevents diet-induced obesity, improves glucose tolerance, and increases exercise capacity. Circulating MOTS-c levels decline with age in humans and correlate with insulin sensitivity in published observational studies.

What is NOT proven

No completed Phase 2 or Phase 3 human efficacy trials. Optimal dosing, route, and long-term safety in humans are unknown. Whether the rodent metabolic and exercise-capacity effects translate to humans at safe doses is unstudied.

Open research questions

Tissue distribution and bioavailability of injected MOTS-c in humans, whether endogenous MOTS-c restoration is achievable through lifestyle intervention versus exogenous supply, and any oncological signal given AMPK and growth-pathway involvement.

Regulatory status

Not approved by any major regulator.

All Proteus® compounds are sold strictly for in-vitro research. Nothing on this page is medical advice, a treatment claim, or a recommendation for human use. Where compounds are licensed medicines in any jurisdiction, that approval applies to the licensed product supplied through a regulated pharmacy — not to research-grade material.