Overview
MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the 12S ribosomal RNA gene of the human mitochondrial genome. It was identified in 2015 as a member of the emerging class of mitochondria-derived peptides (MDPs). Unlike nuclear-encoded peptides, MOTS-c is translated within the mitochondria and subsequently translocated to the cytoplasm and nucleus, where it functions as a retrograde mitochondrial signal. MOTS-c is responsive to metabolic stress, exercise, and caloric restriction, and its circulating levels in humans decline with age and are reduced in individuals with metabolic dysfunction.
Mechanism
MOTS-c activates the AMP-activated protein kinase (AMPK) pathway, a master regulator of cellular energy homeostasis. AMPK activation by MOTS-c promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis while suppressing anabolic pathways that consume ATP. Research has shown that MOTS-c inhibits the folate cycle and de novo purine biosynthesis, leading to AICAR accumulation, an endogenous AMPK activator. In the nucleus, MOTS-c interacts with the antioxidant response element (ARE) binding protein Nrf2, upregulating cytoprotective and antioxidant gene programs. In skeletal muscle models, MOTS-c enhances insulin-stimulated glucose uptake independently of upstream insulin receptor signaling.
Research Areas
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Metabolic & Insulin Sensitivity Research
MOTS-c has been studied for its ability to improve insulin sensitivity and glucose uptake in skeletal muscle cell models and rodent models of diet-induced insulin resistance.
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Exercise Biology Research
Research has examined MOTS-c as a potential exercise mimetic, with studies showing that exogenous MOTS-c administration recapitulates some metabolic adaptations associated with physical exercise in sedentary animal models.
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Aging & Longevity Research
As a mitochondria-derived signal whose levels decline with age, MOTS-c has been studied in the context of aging biology, with research examining its effects on healthspan and age-related metabolic decline in animal models.
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Cellular Stress Response Research
Studies have explored MOTS-c's role in coordinating the mitochondrial stress response, including its activation of Nrf2-dependent antioxidant programs and its effects on cellular resilience under nutrient deprivation and oxidative stress conditions.
Storage
Store lyophilized at -20°C in a desiccated environment. Reconstitute with sterile bacteriostatic water. Stable at 4°C for up to 14 days once reconstituted. Avoid repeated freeze-thaw cycles.