MOTS-c

Overview

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a mitochondria-derived peptide encoded within the mitochondrial genome. It is one of the first identified mitochondrial-derived peptides (MDPs) with systemic metabolic signaling activity, positioning it at the intersection of mitochondrial biology, aging research, and metabolic science.

Mechanism of Action

MOTS-c activates AMPK (AMP-activated protein kinase), the master metabolic sensor that regulates energy homeostasis at the cellular level. Through AMPK activation, it promotes glucose uptake in skeletal muscle, enhances fatty acid oxidation, and improves mitochondrial function. MOTS-c also influences the folate-methionine cycle, affecting one-carbon metabolism and epigenetic regulation.

Research Context

Studies in animal models have demonstrated that MOTS-c administration improves insulin sensitivity, reduces diet-induced obesity, and enhances exercise capacity. Notably, circulating MOTS-c levels decline with age, suggesting it may play a role in age-related metabolic decline. Exercise has been shown to increase endogenous MOTS-c expression, linking it to the molecular benefits of physical activity.

Key Research Areas

Considerations for Researchers

MOTS-c is a relatively small peptide (16 amino acids) with good stability in lyophilized form. Reconstitute with bacteriostatic water and store refrigerated. Verify sequence integrity through mass spectrometry given the short chain length.