Scientific Reference
MOTS-c
Evidence profile: Preclinical, with limited uncontrolled human reports
MOTS-c is a 16-residue peptide encoded by a short open reading frame within the mitochondrial gene for 12S ribosomal RNA. It belongs to the mitochondrial-derived peptides, a small group that also includes humanin, which is encoded in the 16S rRNA gene. Since it was first described in the mid-2010s it has been studied mainly in cultured cells and in mice, with attention to glucose and lipid handling in skeletal muscle and to cellular responses to metabolic stress. Human data are limited and consist mostly of measurements of its circulating levels in observational studies.
Mechanism of Action
The first cell and mouse studies reported that MOTS-c inhibits the folate pathway and, with it, de novo purine synthesis, so that the purine intermediate AICAR accumulates. This nucleotide mimics AMP and activates AMP-activated protein kinase (AMPK), a sensor of cellular energy status. Later work reported that under metabolic or oxidative stress the peptide moves from the cytoplasm into the nucleus, where it associates with transcription factors including NRF2 and alters the expression of stress-response genes. Most of this mechanistic evidence comes from cell and rodent models, and human mechanistic data are scarce.
Molecular Information
- Type: Mitochondrial-derived peptide (MDP)
- Length: 16 amino acids
- Molecular weight: 2174.6 g/mol
- Molecular formula: C101H152N28O22S2