The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
Summary
This landmark study reported the discovery and characterization of MOTS-c (Mitochondrial Open reading frame of the Twelve S rRNA type-c), a 16-amino acid peptide encoded within the mitochondrial genome. MOTS-c was shown to regulate metabolic homeostasis through AMPK activation, targeting the methionine-folate cycle and de novo purine biosynthesis, and preventing diet-induced obesity and insulin resistance in mice.
Key Findings
- MOTS-c is a novel mitochondria-derived peptide encoded in the 12S rRNA gene of mitochondrial DNA, representing a new class of mitochondrial signaling molecules
- MOTS-c activates AMPK and regulates metabolic homeostasis by targeting the methionine-folate cycle and inhibiting de novo purine biosynthesis
- Systemic administration of MOTS-c prevented age-dependent and high-fat-diet-induced insulin resistance and obesity in mice
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View all →Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging
Wan W, Zhang L, Chen Y, et al.
Journal of Translational Medicine
Comprehensive review of MOTS-c as a mitochondrial-derived peptide that acts through the Folate-AICAR-AMPK signaling pathway. Summarizes evidence for MOTS-c's roles in metabolic homeostasis, stress response, exercise adaptation, and aging, positioning it as a key mitochondrial signaling molecule with broad therapeutic potential.
- MOTS-c acts primarily through the Folate-AICAR-AMPK signaling pathway
- Regulates metabolic homeostasis, insulin sensitivity, and inflammatory responses
MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling Pathway in Diabetic Rats
Li S, Lu H, Lu J, et al.
Frontiers in Endocrinology
Showed that MOTS-c treatment restores cardiac function in diabetic rats through activation of the NRG1-ErbB4 signaling pathway. MOTS-c improved cardiac structure and function comparably to exercise, and the combination of MOTS-c plus exercise produced additive cardioprotective benefits.
- MOTS-c restored cardiac function in diabetic rats via NRG1-ErbB4 pathway activation
- Effects were comparable to those achieved by exercise alone
The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity
Kim SJ, Miller B, Mehta HH, et al.
Physiological Reports
Demonstrated that MOTS-c treatment improves insulin sensitivity in diet-induced obese mice and significantly alters plasma metabolite profiles. MOTS-c reduced sphingolipid, monoacylglycerol, and dicarboxylate metabolites while improving glucose tolerance, suggesting metabolic reprogramming as a key mechanism of action.
- MOTS-c improved insulin sensitivity and glucose tolerance in diet-induced obese mice
- Significantly altered plasma metabolome including reduced sphingolipids and monoacylglycerols
DOI: 10.14814/phy2.14171