Metabolic and Fat Loss · 2018

MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism

MOTS-c: um novo peptídeo derivado mitocondrial que regula o metabolismo muscular e adiposo

Kim KH, Son JM, Benayoun BA, Lee C

Free Radic Biol Med

DOI: 10.1016/j.freeradbiomed.2018.09.004 PubMed: 30213684

Summary

This comprehensive review, published by the group that discovered MOTS-c, synthesized advances in understanding this mitochondrial-derived peptide since its discovery in 2015. The article examined the molecular mechanisms, physiological functions, and therapeutic potential of MOTS-c in the context of muscle and fat metabolism.

The authors detailed how MOTS-c regulates energy metabolism through multiple pathways:

  • AMPK activation and modulation of folate metabolism in skeletal muscle
  • Regulation of mitochondrial biogenesis and oxidative capacity
  • Influence on lipid metabolism in adipose tissue, promoting browning of white adipose tissue
  • Modulation of the inflammatory response associated with obesity

The review also explored the connection between MOTS-c and aging, highlighting that circulating MOTS-c levels decline with age in parallel with the decline of mitochondrial function. Genetic variants in the mitochondrial MOTS-c gene (m.1382A>C) were associated with increased risk of type 2 diabetes in Japanese populations, providing genetic evidence for its metabolic relevance.

The authors proposed that MOTS-c represents a new class of mitochondrial endocrine signaling molecules with potential to treat obesity, type 2 diabetes, and sarcopenia associated with aging. The review positions MOTS-c at the intersection of mitochondrial biology, metabolism, and aging, consolidating it as a promising therapeutic target.

Related Peptide

MOTS-C

Mitochondrial ORF of the Twelve S rRNA Type-C

Mitochondrial peptide that improves insulin sensitivity and metabolic flexibility. Exercise mimetic properties. Acts on the AMPK pathway.