Scientific Reference
MOTS-c
Evidence profile: Preclinical, with limited uncontrolled human reports
MOTS-c is unusual in where its code is stored: a 16-residue peptide read from a short open reading frame inside the mitochondrial gene for 12S ribosomal RNA, not from the nuclear genome. It is a mitochondrial-derived peptide, a small group that also includes humanin, which comes from the 16S rRNA gene. It was described in the mid-2010s and has been studied largely in cultured cells and mice, with attention on how skeletal muscle handles glucose and lipids and how cells respond to metabolic stress. Human data are limited, mainly observational measurements of circulating levels.
Mechanism of Action
The first cell and mouse studies reported that MOTS-c inhibits the folate pathway and thereby de novo purine synthesis, so that the intermediate AICAR builds up. AICAR resembles AMP and activates AMP-activated protein kinase (AMPK), a sensor of cellular energy. Later work reported that under metabolic or oxidative stress the peptide travels from cytoplasm to nucleus, where it associates with transcription factors including NRF2 and changes expression of stress-response genes. Nearly all of this mechanistic evidence comes from cell and rodent models, and human mechanistic data are scarce.
Molecular Information
- Type: Mitochondrial-derived peptide (MDP)
- Molecular weight: 2174.6 g/mol
- Molecular formula: C101H152N28O22S2