MOTS-c

MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome. Since its discovery, MOTS-c has been studied as a signaling molecule that communicates between mitochondria and the nucleus, influencing whole-body metabolism. Research interest centers on its regulation of glucose handling, insulin sensitivity, and adaptive responses to metabolic and physical stress.

MOTS-c appears to modulate metabolic flexibility through activation of AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. Upon metabolic stress, MOTS-c can translocate to the nucleus and influence gene expression programs related to antioxidant defense and metabolic adaptation. Studies examine how exercise, aging, and metabolic disease alter circulating and tissue MOTS-c levels, and how supplementation with the synthetic peptide affects glucose uptake and mitochondrial function in preclinical models.

• Insulin sensitivity, glucose uptake, and skeletal muscle metabolism.
• Exercise adaptation and mitochondrial-to-nuclear retrograde signaling.
• Age-related changes in circulating MOTS-c and mitochondrial peptide biology.
• Adipose tissue metabolism and systemic energy expenditure.
• Cellular stress responses and antioxidant gene programs.

• Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 2015.
• Reynolds JC et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications, 2021.
• Kim SJ, Xiao J, Wan J, Cohen P, Yen K. Mitochondrially derived peptides as novel regulators of metabolism. Journal of Physiology, 2017.