MOTS-c

Mitochondrial DNA was long understood to encode only respiratory chain subunits and the RNA needed to make them. MOTS-c — Mitochondrial ORF of the 12S rRNA type-c — is a short open reading frame within the 12S rRNA gene, and its discovery established that mitochondria also encode signalling peptides.

That reframing is most of its significance. It makes the mitochondrion a source of information for the rest of the cell, not merely a consumer of it.

MOTS-c translocates to the nucleus under metabolic stress and influences stress-responsive gene expression — communication travelling from organelle to nucleus, the reverse of the usual direction. Research areas:

• AMPK activation and cellular energy sensing

• The folate-methionine cycle, its reported metabolic point of action

• Insulin sensitivity and glucose handling in animal models

• Exercise physiology, where circulating MOTS-c changes measurably with activity

• Mitochondrial-nuclear communication as a general mechanism

SS-31 acts on mitochondrial structure where MOTS-c acts as a signal from mitochondria. AICAR activates AMPK by a different route, and is the standard comparator for that pathway.