MOTS-c

Molecular Specifications

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome — specifically within the 12S ribosomal RNA small subunit region. Discovered in 2015 by a research team at the USC Leonard Davis School of Gerontology, MOTS-c represents a new class of endogenous signaling molecules termed mitochondria-derived peptides (MDPs) that communicate metabolic status between mitochondria and the nucleus.

MOTS-c is the only known peptide encoded by the mitochondrial genome that translocates to the nucleus under cellular stress conditions, where it regulates nuclear gene expression related to metabolic homeostasis. This mitochondria-to-nucleus signaling function is mechanistically unique among known endogenous peptides.

AMPK Activation Mechanism

In cell culture and animal models, MOTS-c has been observed to activate AMPK (AMP-activated protein kinase) — the master energy-sensing kinase that responds to low ATP conditions. Specifically, MOTS-c research has shown interactions with the folate cycle and one-carbon metabolism, generating AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), an endogenous AMPK activator.

AMPK activation downstream effects studied in MOTS-c research include: GLUT4 translocation and glucose uptake in muscle cells, fatty acid oxidation pathway upregulation, mitochondrial biogenesis via PGC-1α signaling, and mTOR inhibition.

↗ Lee C et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis. Cell Metabolism. PubMed: 25738459

Research Applications

• AMPK signaling pathway activation studies in cell culture
• Mitochondria-to-nucleus retrograde signaling research
• Glucose metabolism and insulin sensitivity pathway studies
• Aging biology and longevity research in animal models
• Exercise physiology pathway research
• One-carbon metabolism and folate cycle research