# MOTS-c

> Evidence tier C — Animal data · Metabolic · reviewed 2026-11-08
> Source page: https://peptidemeta.com/p/mots-c/

Also known as: MOTS-c, Mitochondrial ORF of the 12S rRNA type-c

## Quick answers

**What is MOTS-c?**

A mitochondrial-derived peptide that regulates metabolic homeostasis and insulin sensitivity.

**How strong is the evidence for MOTS-c?**

Tier C (animal data) on the peptidemeta evidence scale. Interventional evidence is from rodent studies (e.g. Lee et al., Cell Metab 2015); human data are observational measurements of circulating levels, with no published human trial of MOTS-c itself.

**Is MOTS-c FDA-approved?**

No. MOTS-c is not approved by the FDA for any use.

**Is MOTS-c banned in sport?**

Yes. MOTS-c is prohibited in sport by the World Anti-Doping Agency under S4 (hormone and metabolic modulators).

**How does MOTS-c work?**

MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial 12S rRNA gene. It translocates to the nucleus during metabolic stress and activates AMPK signaling, which promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis.

**What is known about the safety of MOTS-c?**

Endogenous mitochondrial-derived peptide with naturally declining levels during aging. Limited formal human safety data from interventional use.

## Key facts

- **Evidence tier:** C (Animal data)
- **FDA:** not approved
- **WADA:** prohibited (S4)
- **Peptide:** yes
- **Sequence:** MRWQEMGYIFYPRKLR (16 residues)
- **Formula:** C101H152N28O22S2
- **Molecular weight:** 2174.6 g/mol
- **Discovered:** 2015 — Identified as a peptide encoded in the mitochondrial 12S rRNA gene (Lee et al., Cell Metab 2015).
- **Routes studied:** Subcutaneous, Intramuscular

## Overview

A mitochondrial-derived peptide that regulates metabolic homeostasis and insulin sensitivity. It acts as an exercise mimetic, activating AMPK signaling pathways.

## Mechanism

MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial 12S rRNA gene. It translocates to the nucleus during metabolic stress and activates AMPK signaling, which promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. It also regulates the folate-methionine cycle, affecting cellular methylation and nucleotide synthesis.

## Effects reported in research

_Reported outcomes, not promises; see the evidence tier._

- Improved insulin sensitivity
- Enhanced mitochondrial function
- Exercise-mimetic AMPK activation
- Protection against metabolic stress

## Safety & unknowns

Endogenous mitochondrial-derived peptide with naturally declining levels during aging. Limited formal human safety data from interventional use. Preclinical studies suggest good tolerability. Not FDA-approved.

## Studies

- Lee C, Zeng J, Drew BG, et al. (2015). *The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance*. Cell Metabolism. Preclinical. https://pubmed.ncbi.nlm.nih.gov/25738459/
  Discovery paper identifying MOTS-c as a 16-amino-acid peptide encoded in the mitochondrial 12S rRNA that acts on the folate cycle to activate AMPK; treatment prevented age-dependent and diet-induced insulin resistance and diet-induced obesity in mice.

## Status sources

- [PubChem CID 146675088 — MOTS-c](https://pubchem.ncbi.nlm.nih.gov/compound/146675088)
- [Lee et al., Cell Metab 2015 (discovery)](https://pubmed.ncbi.nlm.nih.gov/25738459/)
- [WADA Prohibited List 2026 (S4.4.1, named)](https://www.wada-ama.org/en/resources/world-anti-doping-code-and-international-standards/prohibited-list)

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Educational reference only — not medical advice. No dosing information is published. Tiers rate the strength of published evidence, not effectiveness or safety.