MOTS-c
preclinicalAlso known as: Mitochondrial ORF of the twelve S c
MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded by the mitochondrial 12S rRNA gene. Its primary mechanism involves activation of AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. This activation enhances insulin sensitivity, promotes glucose uptake, and stimulates fatty acid oxidation, thereby improving metabolic flexibility. MOTS-c also modulates nuclear gene expression related to mitochondrial function and stress responses, suggesting a retrograde signaling role from mitochondria to the nucleus. Preclinical studies in rodent models demonstrate that MOTS-c administration reduces diet-induced obesity, improves glucose tolerance, and reverses age-related insulin resistance. It has been shown to increase metabolic rate and protect against high-fat diet-induced hepatic steatosis. Additionally, MOTS-c levels decline with age in humans, and its exogenous supplementation in aged mice restores metabolic function, implicating it in the aging process. However, all current evidence is derived from cell culture and animal models. Clinical relevance remains speculative, as no human trials have been published. Potential applications include metabolic disorders such as type 2 diabetes, obesity, and sarcopenia, but safety, pharmacokinetics, and efficacy in humans are unestablished. The peptide's mitochondrial origin and AMPK-dependent effects position it as a candidate for metabolic and aging-related interventions, pending rigorous clinical validation. For research purposes only — not medical advice.
Key data
C101H152N28O22S2Research & studies
MOTS-c upregulation in endothelial cells correlates with barrier preservation and reduced oxidative stress in rat LIRI models.; Hypoxia-reoxygenation triggers ROS-dependent phosphorylation of MYH9 at Ser1943 via CK2A, enabling MOTS-c nuclear transport.; MOTS-c directly interacts with promoters of antioxidant genes (e.g., HMOX1, NQO1) containing antioxidant response elements.; Serum MOTS-c increments within 24 h post-CPB outperform traditional biomarkers in predicting ARDS incidence (AUC = 0.885).
High glucose levels activate the NLRP3 inflammasome and increase ROS, leading to myocardial injury.; MOTS-c treatment (0.5 mg/kg/day for 8 weeks) reduced ROS/TXNIP/NLRP3 pathway protein expression.; MOTS-c inhibits the diabetic myocardial inflammatory response via the ROS/TXNIP/NLRP3 pathway.; MOTS-c alleviates myocardial damage in diabetic rats.
MOTS-c levels are decreased in serum and tumor tissues of ovarian cancer patients and correlate with poor prognosis.; Exogenous MOTS-c inhibits ovarian cancer cell proliferation, migration, and invasion, and induces cell cycle arrest and apoptosis.; MOTS-c promotes LARS1 ubiquitination and degradation by competing with deubiquitinase USP7 for binding to LARS1.; MOTS-c exhibits anti-tumor effects on ovarian cancer growth in vivo without systemic toxicity.
MOTS-c directly binds and activates CK2 in cell-free systems.; MOTS-c administration prevents muscle atrophy and enhances glucose uptake in mice, effects blocked by suppressing CK2.; MOTS-c has tissue-specific effects, activating CK2 in muscle but suppressing it in fat via differential protein interactions.; The K14Q MOTS-c variant has reduced CK2 binding and is linked to higher sarcopenia and T2D risk in males, with sex-specific effects in females.
MOTS-c levels positively correlated with mitochondrial abundance and TRIM72 in humans.; Moderate-intensity exercise increased MOTS-c secretion and TRIM72 interaction, improving sarcolemma integrity.; MOTS-c promoted TRIM72 trafficking to the injured membrane but required TRIM72 for membrane repair.; MOTS-c interacted with phosphatidylinositol (4,5) bisphosphate to enhance vesicle fusion with the membrane.
Frequently asked questions
What is MOTS-c?
MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded by the mitochondrial 12S rRNA gene. Its primary mechanism involves activation of AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. This activation enhances insulin sensitivity, promotes glucose uptake, and stimulates f
How does MOTS-c work?
Mitochondrial-derived 16-aa peptide that activates AMPK and improves insulin sensitivity and metabolic homeostasis.
What is the research status of MOTS-c?
MOTS-c is currently classified as preclinical, with 246 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of MOTS-c?
MOTS-c has a molecular weight of approximately 2174.6 g/mol (formula C101H152N28O22S2).
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