MOTS-c
MOTS-c is a 16-amino-acid mitochondrial-derived peptide, encoded within the mitochondrial 12S rRNA gene, that functions as an exercise-responsive metabolic regulator with strong preclinical (mostly rodent) evidence for effects on insulin sensitivity and muscle bioenergetics, while human evidence as of 2026 remains largely observational/correlational rather than from controlled administration trials.
This page is a research-orientation summary, not a dosing guide. For anything beyond general background, read the primary literature or talk to a qualified clinician — specifics like amount, frequency, or administration aren't something we publish here.
What it does & how it works
MOTS-c is translated from an alternative open reading frame within mitochondrial 12S rRNA and is exported to the cytosol, where metabolic or oxidative stress promotes its translocation to the nucleus to regulate nuclear gene expression, including antioxidant-response programs. In skeletal muscle and liver it activates AMP-activated protein kinase (AMPK), driving downstream effects on glucose uptake, fatty-acid oxidation, and PGC-1α-linked mitochondrial biogenesis. This positions MOTS-c as a mitochondrial-to-nuclear retrograde signaling peptide that couples mitochondrial status to cellular metabolic adaptation.
Typical results seen in research
In mice, MOTS-c administration improves insulin sensitivity, limits diet-induced obesity, and restores age-related declines in grip strength, gait, and treadmill capacity even when treatment begins late in life; it has also shown activity in rodent models of neuropathic pain and muscle bioenergetics via AMPK-dependent pathways. In humans, circulating MOTS-c falls with age and rises acutely with aerobic and resistance exercise, but these remain largely correlational observations, and controlled human trials of exogenous MOTS-c administration are still limited, so effects on human metabolic or physical-performance outcomes are not yet firmly established.
How it’s commonly used
MOTS-c has been administered experimentally by subcutaneous or intraperitoneal injection in animal studies, and early human investigational work has also used subcutaneous injection. It has no FDA-approved indication and no standardized clinical administration protocol.
- Cell Metabolism · 2015 The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
- International Journal of Molecular Sciences · 2022 MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases
- ACS Chemical Neuroscience · 2023 Mitochondrial-Derived Peptide MOTS-c Ameliorates Spared Nerve Injury-Induced Neuropathic Pain in Mice by Inhibiting Microglia Activation and Neuronal Oxidative Damage in the Spinal Cord via the AMPK Pathway
- Free Radical Biology and Medicine · 2026 MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner
Curated from published literature for research orientation. Not an exhaustive review, and not a substitute for reading primary sources.