MOTS-C Research Peptide

MOTS-c is a synthetic research peptide consisting of a 16-amino acid sequence (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg) that originates from a short open reading frame encoded within the mitochondrial 12S rRNA gene. Unlike nuclear-encoded peptides, MOTS-c is classified as a mitochondria-derived peptide and has been examined for its role in intracellular metabolic regulation. Preclinical research has shown that MOTS-c participates in pathways associated with cellular energy balance and mitochondrial function, including activation of AMP-activated protein kinase (AMPK). Experimental models have also explored its involvement in mitochondrial stress responses and adaptive metabolic signaling. Because of these properties, MOTS-c is frequently used in laboratory studies focused on metabolism, aging biology, and mitochondria-to-nucleus communication mechanisms.

Evidence classification: MOTS-c mechanistic findings are from cell and mouse models; human data are mainly observational measurements of endogenous levels.

The 2015 discovery paper reported that MOTS-c affected folate-cycle and purine metabolism in cultured cells and activated AMP-activated protein kinase (AMPK). Mouse studies in the same paper examined metabolic endpoints. A 2018 study reported that MOTS-c translocates to the nucleus under metabolic stress in cell models, and a 2021 study examined its relationship to physical capacity in aging mice and measured endogenous levels in human muscle and plasma after exercise.

• Inhibition of the folate cycle and de novo purine biosynthesis, leading to AICAR accumulation and AMPK activation (in vitro).
• Stress-induced nuclear translocation and interaction with transcription factors such as NRF2 (in vitro).
• Regulation of nuclear genes containing antioxidant response elements (in vitro).

Read the full MOTS-c research overview in the FuelX Research Library.