MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino acid peptide encoded by the mitochondrial DNA, specifically within the 12S rRNA region.
 It was discovered in 2015 and functions as a signaling molecule that communicates between the mitochondria and the nucleus to maintain cellular and metabolic health.
 MOTS-c is primarily produced in response to metabolic stress and exercise, and its expression decreases with aging.
 It translocates to the nucleus where it regulates the expression of genes involved in stress adaptation, energy metabolism, and insulin sensitivity, particularly through the AMPK/PGC-1α pathway.
The peptide plays a crucial role in regulating metabolic homeostasis, improving insulin sensitivity, enhancing glucose metabolism in skeletal muscle, and promoting fat breakdown.
 It acts as an exercise mimetic, meaning it can replicate some of the beneficial effects of physical activity, such as improved physical performance and endurance.
 Studies in mice have shown that MOTS-c treatment improves physical function across all ages and helps maintain muscle homeostasis.
 It also influences multiple tissues, including adipose tissue, liver, and the cardiovascular system, contributing to systemic metabolic regulation.
MOTS-c has shown therapeutic potential for various conditions, including type 2 diabetes, obesity, insulin resistance, cardiovascular disease, and age-related pathologies such as neurodegeneration and osteoporosis.
 It helps mitigate age-related decline by promoting mitochondrial health and energy balance.
 However, despite its promising effects, MOTS-c is not currently approved by any regulatory body to treat any medical condition.
 Furthermore, it is banned by the World Anti-Doping Agency (WADA) for use in sports, with the ban taking effect in 2024.
 The specific mechanism by which exercise regulates MOTS-c expression is not fully understood, and its response to exercise may vary based on ethnicity or underlying health conditions.