MOTS-C (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a peptide derived from the mitochondria, first identified in 2015. Encoded within the 12S rRNA gene of the mitochondrial genome, this 16-amino acid peptide functions as a key mitochondrial-encoded regulatory signal. MOTS-C plays a significant role in linking mitochondrial activity to metabolic regulation. It primarily targets skeletal muscle, where it activates the AMPK (AMP-activated protein kinase) pathway—an essential mechanism for maintaining cellular energy balance.

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