MOTS-c
16-amino-acid mitochondrial-derived peptide encoded in mitochondrial 12S rRNA; studied for metabolic regulation in rodents.
Overview
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded by a short open reading frame in the mitochondrial 12S ribosomal RNA gene. It was first described in 2015 by the laboratory of Pinchas Cohen as a mitochondrial-derived peptide with metabolic actions. Subsequent cell and rodent studies have examined its effects on insulin sensitivity, exercise metabolism, and age-related metabolic decline. Human data remain very limited.
Mechanism
MOTS-c is reported to translocate into the nucleus under metabolic stress and regulate gene expression, including activation of AMPK and downstream pathways that favor fatty-acid oxidation and improve insulin action in skeletal muscle. It is also described as responding to exercise, with circulating levels changing after physical activity in some human studies, though its full receptor and signaling biology is still being characterized.
Dosing
In published rodent studies MOTS-c is administered by injection, typically intraperitoneally at microgram-per-kilogram doses specified per protocol. No established human research dosing exists, and published human intervention data are minimal.
Expected Effects
- improved insulin sensitivity and glucose disposal in rodent metabolic studies
- increased fatty-acid oxidation and metabolic adaptations in muscle models
- protection against age- and diet-related metabolic decline in mouse studies
- changes in circulating MOTS-c after exercise reported in human observational studies
Side Effects & Tolerability
Tolerability information derives mainly from rodent studies, which have not reported major toxicity. As an endogenous mitochondrial peptide, immunogenicity is considered a low theoretical risk, but no systematic human safety data exist.
Storage
Lyophilized MOTS-c should be stored desiccated, protected from light, and kept frozen at -20 deg C or below. After reconstitution, refrigerate at 2-8 deg C and use within a short window, avoiding repeated freeze-thaw cycles.