The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance — VialBase Research
Discovery paper for MOTS-c as a mitochondrial-derived peptide
- Discovery paper for MOTS-c as a mitochondrial-derived peptide
- MOTS-c encoded within the mitochondrial 12S rRNA gene
- Activates AMPK via inhibition of the folate cycle (AICAR accumulation)
- Prevented age-dependent and high-fat-diet-induced insulin resistance in mice
- Improved glucose tolerance and reduced body weight
- Establishes mitochondria as active signaling organelles
Summary
Landmark discovery paper identifying MOTS-c as a novel mitochondrial-derived peptide encoded within the mitochondrial genome (12S rRNA). Demonstrates that MOTS-c regulates metabolic homeostasis by targeting the folate-methionine cycle, leading to AMPK activation. Exogenous MOTS-c administration prevented both age-dependent and high-fat-diet-induced insulin resistance in mice, and improved glucose tolerance.
Key Findings
- MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial genome
- Acts as a retrograde signal from mitochondria to the nucleus
- Inhibits AICAR transformylase (ATIC) in the folate cycle → AICAR accumulation → AMPK activation
- Prevents age-dependent insulin resistance when administered exogenously
- Prevents high-fat-diet-induced obesity and insulin resistance
- Improves glucose tolerance in treated mice
- Paradigm shift: mitochondria are not just powerhouses but active signaling organelles
Relevance to MOTS-c
This is the foundational paper for MOTS-c — all subsequent research builds on this discovery. Establishes the core mechanism (folate cycle → AICAR → AMPK), the metabolic phenotype (insulin sensitization, anti-obesity), and the conceptual framework (mitochondrial-derived peptides as retrograde signals). Essential reference for understanding MOTS-c’s biological rationale.
Citation
Lee C, et al. Cell Metab. 2015;21(3):443-454. PMID: 25738459
See Also
- Parent compound: MOTS-c