MOTS-C

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid mitochondrial-derived peptide (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg) encoded within the mitochondrial 12S rRNA gene. Unlike nuclear-encoded peptides, MOTS-c originates from mitochondrial DNA and is investigated in laboratory research for its role in retrograde signaling, whereby mitochondrial activity influences nuclear gene expression. In preclinical and controlled experimental systems, MOTS-c is studied for its regulation of cellular metabolism through AMP-activated protein kinase (AMPK) activation and maintenance of mitochondrial homeostasis.

In vitro systems and structured clinical investigations evaluate endpoints including AMPK phosphorylation activity, glucose-uptake dynamics, insulin-sensitivity markers, mitochondrial biogenesis indicators, oxidative stress biomarkers, and transcriptional profiles associated with metabolic flexibility. Additional research explores nuclear translocation under stress conditions, inflammatory signaling modulation, and gene-expression changes linked to energy regulation and adaptive cellular responses.