CAS Number: 1627580-64-6
Molecular Formula: C₁₀₀H₁₇₃N₃₃O₃₁S
Molecular Weight: 2174.74 g/mol
Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (16 amino acids)
What is MOTS-c?
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-C) is a peptide encoded by a short open reading frame within the mitochondrial 12S rRNA gene. It is significantly expressed in response to stress or exercise and translocates to the nucleus, where it regulates the expression of stress adaptation-related genes. PubMed Central It acts as a peptide hormone detected across various tissues and organs, functioning as a retrograde signaling molecule that transmits messages from the mitochondria to the nucleus, affecting the physiological metabolism of the body. PubMed Central
Areas of Active Research:
1. Insulin Resistance & Metabolic Health
MOTS-c has been shown to improve glucose metabolism in skeletal muscle, indicating benefits for diseases such as diabetes and obesity. PubMed Central It influences insulin-regulated pathways, reducing insulin resistance and promoting glucose uptake in skeletal muscle cells. Intricateartseminars
2. Anti-Aging & Longevity
Plasma MOTS-c levels decline with age in humans across young (18–30), middle (45–55), and older (70–81) age groups. Two weeks of systemic MOTS-c treatment significantly increased the physical capacity of old mice, allowing them to double their running time on a treadmill and effectively outrun their middle-aged counterparts. e-DMJ
3. Exercise Performance & Muscle Health
MOTS-c is a mitochondrial-encoded, exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan in older mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Nature
4. Cardiovascular Health
In the heart, MOTS-c improves myocardial mechanical efficiency, enhances cardiac systolic function, improves diastolic function, and reduces damage to heart structure and function from type 2 diabetes. Exogenous supplementation of MOTS-c also promotes the cardiovascular benefits of exercise. PubMed Central
5. Inflammation
A significant decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines was observed with MOTS-c in mice serum. These analgesic and anti-inflammatory effects appear to work through activation of the AMPK pathway and inhibition of the MAP kinase/c-Fos pathway. PubMed Central
6. Bone Metabolism
Recent studies have revealed that MOTS-c promotes osteoblast proliferation, differentiation, and mineralization, while also inhibiting osteoclast production — mediating the regulation of bone metabolism and bone remodeling. Frontiers
7. Immune Regulation & Diabetes
MOTS-c has a robust immunoregulatory function in autoimmune Type 1 diabetes, with treatment found to prevent the activation of T cells derived from human T1DM patients. e-DMJ
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