MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within the mitochondrial 12S ribosomal RNA gene — making it one of the few proteins encoded by mitochondrial DNA (mtDNA) in the human genome. It was characterised by Lee et al. in 2015 (Cell Metab) as a mitochondria-derived peptide (MDP) that regulates metabolic homeostasis primarily through AMPK activation, folate cycle regulation, and purine synthesis inhibition. Its most notable research property is mimicking the acute metabolic response to exercise — increasing glucose uptake, fatty acid oxidation, and AMPK activity in skeletal muscle — without physical exercise. Circulating MOTS-c declines with age and in insulin-resistant states, positioning it as a candidate longevity and metabolic peptide.
2174.6 g/mol
Molecular weight
AMPK
Primary downstream signal — metabolic master switch
mtDNA
Encoded in 12S rRNA — not nuclear genome
Exercise mimetic
Mimics acute exercise metabolic response
≥99%
Purity — HPLC verified
MOTS-c — Specifications
MOTS-c — specifications
Property
Value
CAS Number
1457186-64-9
Molecular Formula
C₁₀₁H₁₅₄N₃₀O₃₄S
Molecular Weight
2174.6 g/mol
Half-life
~1–2 hr (SC)
Class
Mitochondria-derived peptide (mtDNA-encoded)
Purity
≥99% HPLC verified
COA
Janoshik independent third-party
⚙️
Mechanism of Action — MOTS-c
MOTS-c has a unique, receptor-independent mechanism compared to conventional peptide hormones:
Nuclear translocation: Stress conditions → MOTS-c translocates from mitochondria to nucleus → binds ARE (antioxidant response element) → Nrf2 target gene activation
Insulin sensitisation: Reduces ceramide and diacylglycerol (DAG) accumulation in muscle → reduces IRS-1 serine phosphorylation → improves insulin signalling
Age-related decline: Circulating MOTS-c is 50% lower in older vs younger humans — potential biomarker and therapeutic target
Why MOTS-c is called an exercise mimetic
MOTS-c activates AMPK through the same AICAR pathway used by acute exercise — without muscle contraction or mechanical loading. Injection of MOTS-c in sedentary animals recapitulates several acute exercise responses: GLUT4 translocation to the cell surface, fatty acid oxidation upregulation, and the AMPK-dependent metabolic gene expression programme (PGC-1α, TFAM). This makes it the primary research tool for dissecting exercise-mediated metabolic adaptations from the mechanical/contraction component.
Key Research Studies & Clinical Data
Key MOTS-c research milestones
Study
Model/Finding
Year
Lee et al. — Cell Metab
MOTS-c characterised from mtDNA; AMPK mechanism; obesity/insulin resistance reversal in DIO mice
2015
Kim et al. — Aging Cell
MOTS-c plasma levels decline with age in humans; supplementation extends lifespan in C. elegans
2018
Reynolds et al. — Nat Aging
MOTS-c + exercise synergy in aged mice; MOTS-c translocation to nucleus under stress
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene — one of the few peptides encoded by mitochondrial (not nuclear) DNA. It is a mitochondria-derived peptide (MDP) that activates AMPK, improves insulin sensitivity, and mimics metabolic aspects of acute exercise.
How does MOTS-c activate AMPK?
MOTS-c inhibits AICAR-transformylase in the folate cycle, causing AICAR accumulation. AICAR is a direct AMPK activator — the same pathway used by metformin and AICAR injection. This makes MOTS-c mechanistically upstream of conventional AMPK activators and explains its exercise-mimicking metabolic profile.
Why is MOTS-c called an exercise mimetic?
MOTS-c injection activates the same AMPK-dependent metabolic programme as acute exercise: GLUT4 translocation to the muscle cell surface (glucose uptake), fatty acid oxidation (CPT1 upregulation via pACC), and PGC-1α-driven mitochondrial biogenesis. This occurs without muscle contraction — making MOTS-c the tool for dissecting exercise metabolism from the mechanical stimulus.
Does MOTS-c decline with age?
Yes. Lee et al. and subsequent studies show plasma MOTS-c is approximately 50% lower in older adults compared to younger individuals. This age-related decline correlates with increased insulin resistance and reduced metabolic flexibility.
What formats does QSC supply MOTS-c in?
QSC supplies MOTS-c as lyophilised research vials (40mg per vial) in 10-vial kits (400mg total), ≥99% purity HPLC verified with Janoshik COA. Ships from domestic QSC warehouses in USA, EU, UK, Canada, and Australia.
Research Use Only: All QSC compounds are sold strictly for laboratory research purposes. Not for human use. Not approved by the FDA or equivalent regulatory bodies for human administration. All purchases confirm research intent and compliance with applicable local regulations.
