Definition
A short peptide encoded within mitochondrial DNA, such as humanin or MOTS-c, studied for metabolic signalling.
Mitochondrial-derived peptides are short peptides encoded by small open reading frames within the mitochondrial genome. Humanin, a 24-residue peptide, was identified in 2001 in a screen for factors protecting neurons from Alzheimer's-related insults. MOTS-c, a 16-residue peptide encoded in the 12S rRNA region, was described by Lee et al. in 2015 as a regulator of metabolic homeostasis acting in part through AMPK in mouse models. Both circulate in plasma and have been investigated in rodent models of metabolism and ageing. They are distinct from mitochondria-targeted synthetic peptides such as elamipretide (SS-31), which are not mitochondrially encoded.