MOTS-c: Complete Guide
MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA Type-C) is a mitochondrial-derived peptide consisting of 16 amino acids encoded within the mitochondrial genome. Discovered in 2015 by Dr. Changhan David Lee at the University of Southern California, MOTS-c has generated significant interest for its role in metabolic regulation, exercise mimetic effects, and potential anti-aging applications. It is the first mitochondrial-derived peptide shown to act as a signaling molecule regulating nuclear gene expression.
Last updated: 2026-01-28
Quick Facts
- Category
- therapeutic
- Also Known As
- Mitochondrial ORF of the Twelve S rRNA Type-C
- Related Goals
- fat loss, anti aging
Who Researches MOTS-c?
MOTS-c is researched by people interested in metabolic health, fat loss, and exercise performance — particularly those looking for a peptide that mimics some of the metabolic benefits of exercise. It's popular with people who want to improve insulin sensitivity, support body composition changes, or complement their fitness routine. MOTS-c is also studied in anti-aging contexts since levels decline naturally with age. If you're interested in metabolic optimization but don't want the appetite and GI effects of GLP-1 agonists like tirzepatide, MOTS-c targets a completely different pathway (AMPK activation).
Related Resources
- Stacks: Fat Loss Stack
MOTS-c (10mg)
We may earn a commission if you purchase through this link, at no extra cost to you.
What Is MOTS-c?
MOTS-c represents a paradigm shift in understanding mitochondrial biology. Previously, mitochondrial DNA was thought to encode only proteins involved in oxidative phosphorylation (energy production). The discovery that mitochondria encode signaling peptides like MOTS-c that regulate nuclear gene expression opened an entirely new area of biology — mitonuclear communication.
MOTS-c is released from mitochondria into the cytoplasm and bloodstream, where it acts as a retrograde signal from mitochondria to the nucleus. During metabolic stress (such as exercise), MOTS-c translocates to the nucleus where it directly regulates gene expression related to metabolism, stress adaptation, and cellular homeostasis.
Mechanism of Action
- AMPK activation: MOTS-c activates AMP-activated protein kinase, the master metabolic sensor that promotes glucose uptake, fat oxidation, and mitochondrial biogenesis
- Folate metabolism: MOTS-c regulates the folate-methionine cycle, affecting de novo purine biosynthesis and one-carbon metabolism
- Insulin sensitivity: Improves glucose disposal and insulin signaling in skeletal muscle
- Exercise mimetic: Activates metabolic pathways normally stimulated by physical exercise, including AMPK-PGC1α signaling
- Nuclear gene regulation: Translocates to the nucleus during stress to directly modulate gene expression related to metabolic adaptation
Researching peptides? We did the hard part.
Get our free Peptide Starter Kit — the 5 most researched compounds, simplified into one actionable guide.
Dosage Overview
MOTS-c research dosing (based on animal studies and early human research):
- Subcutaneous: 5–10 mg daily or every other day
- Research cycles: 4–8 weeks
Dosing is primarily extrapolated from animal studies (typically 5mg/kg in mice). Human clinical trials are underway but dosing guidelines remain preliminary. Use the peptide calculator for reconstitution.
Side Effects & Safety
As a naturally occurring peptide encoded by human mitochondrial DNA, MOTS-c is expected to have good biological compatibility. Limited safety data exists:
- Injection site reactions: Mild redness reported
- Blood glucose effects: As an insulin sensitizer, MOTS-c could theoretically cause hypoglycemia in combination with diabetes medications
- Limited human data: Most evidence comes from animal studies and cell culture