MOTS-c (Mitochondrial ORF of the 12S rRNA Type-C) is a 16-amino acid mitochondrial-derived peptide encoded within the mitochondrial genome. It translocates to the nucleus under metabolic stress to regulate gene expression, functions as a mitochondrial hormone in circulation, and declines with age. Below is a curated selection of peer-reviewed studies investigating its properties.
2025
MOTS-c Restores Mitochondrial Respiration in the Type 2 Diabetic Heart
PMC / Frontiers in Physiology
This study demonstrated that MOTS-c treatment restored mitochondrial respiration, reduced fasting blood glucose, and improved cardiac function in type 2 diabetic rats. MOTS-c activated AMPK signalling, improved insulin sensitivity, and upregulated GLUT4 expression in skeletal muscle, positioning it as a promising metabolic research agent.
View Paper →2025
Reduced Serum Levels of MOTS-c in Patients with Obstructive Sleep Apnea
PMC / Sleep and Biological Rhythms
This clinical study investigated the relationship between circulating MOTS-c levels and obstructive sleep apnea severity. Patients with OSA showed significantly reduced serum MOTS-c compared to controls, suggesting MOTS-c may play a role in mediating the metabolic and oxidative stress consequences of sleep-disordered breathing.
View Paper →2023
MOTS-c: A Promising Mitochondrial-Derived Peptide for Therapeutic Exploitation
PMC / Frontiers in Endocrinology
This comprehensive review covers MOTS-c’s discovery, physiological functions, and therapeutic applications across aging, cardiovascular disease, insulin resistance, and inflammation. The authors discuss MOTS-c’s nuclear translocation mechanism under metabolic stress and its potential integration with synthetic biology for clinical development.
View Paper →2022
MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases
PMC / International Journal of Molecular Sciences
This review examines MOTS-c’s role across age-related conditions including diabetes, cardiovascular disease, osteoporosis, postmenopausal obesity, and Alzheimer’s disease. It details how MOTS-c levels decline with age and how supplementation in animal models has demonstrated beneficial effects across multiple disease pathways.
View Paper →2021
MOTS-c is an Exercise-Induced Regulator of Aging Metabolic Homeostasis and Physical Capacity
PMC / Cell Metabolism
This study identified MOTS-c as a mitochondrial-encoded regulator of exercise capacity and metabolic homeostasis. Circulating MOTS-c increased with exercise and declined with age in mice. MOTS-c administration improved physical capacity and reversed age-dependent insulin resistance, supporting its designation as a “mitokine” with systemic regulatory functions.
View Paper →2024
The Correlation Between Mitochondrial Derived Peptide MOTS-c and Metabolic States: A Systematic Review and Meta-Analysis
Diabetology & Metabolic Syndrome (Springer)
This systematic review and meta-analysis synthesised evidence on blood MOTS-c concentrations across metabolic conditions. It found consistent associations between reduced circulating MOTS-c and metabolic dysfunction, supporting MOTS-c as a measurable biomarker and potential therapeutic target in metabolic disease research.
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