MOTS-c

Overview

MOTS-c (Mitochondrial ORF of 12S rRNA type-c) is a 16-amino-acid peptide encoded in the mitochondrial genome — one of the few known peptides translated from mitochondrial DNA. Research suggests MOTS-c activates AMPK signaling, supports insulin sensitivity and glucose metabolism, and may counter age-related metabolic decline. Early human data and animal studies also point to effects on exercise capacity and cellular stress response. MOTS-c remains investigational and is not FDA-approved; the links below connect to our dosage chart and calculator for educational reference only.

Key Information

Mechanism

Activates AMPK through an AICAR-independent pathway, modulates the endothelin A receptor (ETAR), improves mitochondrial energy coupling, and translocates to the nucleus to regulate stress-response gene expression.

Benefits

• Insulin sensitivity support
• Metabolic health research
• Exercise capacity studies
• AMPK activation
• Cellular energy (mitochondrial) support

Side Effects

• Injection-site reactions (redness, bruising)
• Potential allergic reaction
• Long-term safety not established

Contraindications

• Pregnancy or breastfeeding
• Diabetes medication use without medical supervision
• Known mitochondrial disorders — consult specialist

Evidence Summary

Early human and animal research support metabolic effects; no FDA-approved indication.

Research

Preclinical and early human research suggest improved insulin sensitivity, glucose metabolism, and exercise performance. A phase 2a clinical trial has studied fixed-dose MOTS-c protocols for metabolic health.

Safety

Commonly reported side effects are injection-site reactions. Long-term human safety data is limited; no FDA-approved dosing exists.

MOTS-c: Mitochondrial Peptide for Metabolic Health

MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial genome — one of the few peptides known to be translated from mitochondrial DNA rather than nuclear DNA. Research interest centers on metabolic health: AMPK activation, insulin sensitivity, glucose metabolism, and exercise capacity. MOTS-c is investigational and is not FDA-approved. See our MOTS-c dosage chart and MOTS-c calculator for educational reference.

Key Information

• Also known as: MOTS c; Mitochondrial open reading frame of the 12S rRNA type-c
• Sequence: 16 amino acids (mitochondrial-derived)
• Half-life: short (estimated ~1 hour)
• Administration: subcutaneous injection
• Dose range discussed in research: 5-10 mg weekly (research protocols)
• Price range: $1.5–$8.0/mg
• Storage: lyophilized at -20C; reconstituted 2-8C, use within 28 days
• Reconstitution: bacteriostatic water
• US status: research only
• Legal status: not FDA-approved; sold as a research chemical

Mechanism

MOTS-c activates AMPK through an AICAR-independent pathway, modulates the endothelin A receptor (ETAR), improves mitochondrial energy coupling, and can translocate to the nucleus to regulate stress-response gene expression — a unique "mitokine" signaling profile.

Benefits Discussed in Research

• Insulin sensitivity support
• Metabolic health and glucose metabolism research
• Exercise capacity studies
• AMPK activation and cellular energy support

Side Effects

• Injection-site reactions (redness, bruising)
• Potential allergic reaction
• Long-term safety not established

Contraindications

• Pregnancy or breastfeeding
• Diabetes medication use without medical supervision
• Known mitochondrial disorders — consult a specialist

Evidence Summary

Early human research and animal studies support metabolic effects (insulin sensitivity, exercise capacity). A phase 2a clinical trial has examined fixed-dose MOTS-c protocols. No FDA-approved indication exists. MOTS-c was first characterized by Lee et al. (Cell, 2015).

Frequently Asked Questions About MOTS-c

What is MOTS-c?

MOTS-c (Mitochondrial ORF of 12S rRNA type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome. It is studied as a "mitokine" — a mitochondrial signal that can influence cellular energy metabolism, insulin sensitivity, and stress responses.

How does MOTS-c work?

MOTS-c activates AMPK (an energy-sensing enzyme) via a pathway distinct from exercise and metformin-like compounds, modulates the endothelin A receptor, and can enter the nucleus to adjust stress-response gene expression.

What dose is discussed in research?

Commonly discussed research protocols reference 5-10 mg weekly via subcutaneous injection, but there is no FDA-approved dose. Cross-check concentration math with our MOTS-c calculator and read the MOTS-c dosage chart for how these ranges are commonly interpreted. Any decision belongs with a qualified clinician.

Where can I buy MOTS-c?

PepsReview indexes vendor pricing for research peptides. Check the Vendors tab above for cost per milligram, purity, and COA status where available. MOTS-c is sold for research use only.

Is MOTS-c legal?

US regulatory status: research only. MOTS-c is not FDA-approved and is sold as a research chemical.

What are the side effects of MOTS-c?

Reported effects are mainly injection-site reactions; allergic reactions are possible. Long-term human safety data is limited. Review safety data and consult a clinician before any use.

Related Anti-Aging / Mitochondrial Peptides

Other peptides studied for cellular energy and longevity research:

• SS-31 (Elamipretide) — Mitochondrial peptide for cellular protection
• Epithalon — Telomerase-activating longevity peptide
• GHK-Cu — Copper peptide for repair and anti-aging
• KPV — Anti-inflammatory tripeptide

Related Anti-aging / Longevity Peptides

Other peptides in the anti-aging / longevity category that may be of interest for comparative research: