MOTS-c

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded by a short open reading frame within the mitochondrial 12S ribosomal RNA gene. It belongs to a broader family of mitochondrial-derived peptides (MDPs) that also includes humanin and the small humanin-like peptides. First identified in 2015, MOTS-c functions as a mitokine—a mitochondrial-derived signaling peptide that can act both within the cell and systemically as a hormone-like factor. Its expression is induced by exercise, and it is considered an "exercise mimetic" due to its ability to replicate many of the beneficial metabolic effects of physical activity.

MOTS-c exerts its effects through multiple interconnected signaling pathways, with the two most prominent involving activation of AMP-activated protein kinase (AMPK) and direct binding to Casein Kinase 2 (CK2). The primary mechanism involves inhibition of the folate cycle, an intermediate metabolic pathway required for de novo purine synthesis, leading to accumulation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide)—a known endogenous AMPK activator. AMPK activation promotes glucose uptake by stimulating GLUT4 translocation to the cell membrane and enhances fatty acid oxidation. Under metabolic stress, MOTS-c translocates to the nucleus, where it regulates the expression of stress adaptation-related genes with antioxidant response elements (ARE). It also modulates the Nrf2/Keap1 antioxidant pathway and suppresses the NF-κB inflammatory pathway.

• Metabolic Homeostasis and Insulin Sensitivity: Investigated for promoting glucose uptake, improving insulin sensitivity, and reducing obesity and insulin resistance in preclinical models.
• Exercise and Physical Performance: Studied as an "exercise mimetic" for its role in mediating the metabolic effects of exercise in skeletal muscle.
• Aging and Longevity: Explored for promoting healthy aging by enhancing metabolic fitness and physical capacity, with potential applications in delaying age-related physical decline.
• Neuroprotection: Investigated for protective effects against brain injury, neuropathic pain, and neuroinflammation through inhibition of microglia activation and modulation of inflammatory responses.
• Inflammation and Oxidative Stress: Employed in research on anti-oxidative stress, inflammatory diseases, and modulation of the NF-κB pathway.

CAS Number: 1627580-64-6
PubChem CID: 121231475 (also reported as 146675088)
Molecular Formula: C₁₀₁H₁₅₂N₂₈O₂₂S₂
Molecular Weight: 2,174.62 g/mol
Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR)
Purity: ≥ 98% (batch-dependent; refer to Certificate of Analysis)
Form: Lyophilized powder
Storage: Store at ≤ -20°C in a cool, dry place, protected from light and moisture
Solubility: Soluble in sterile water and DMSO; prepare working solutions per laboratory protocol