The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis

Cell Metabolism·2015·Lee C, Zeng J, Drew BG, et al.·Cell Metabolism

This foundational study characterizes MOTS-c as a mitochondria-derived peptide that translocates to the nucleus under metabolic stress and regulates adaptive gene expression. In mice, MOTS-c improved insulin sensitivity and prevented diet-induced obesity, suggesting a role as an exercise mimetic.

Why this research is interesting

This is the original characterization of MOTS-c, a peptide encoded within the mitochondrial genome. It opened a new area of research into mitochondria-derived signaling peptides and their potential relevance to aging and metabolism.

What the research says

The researchers identified MOTS-c as a 16-amino-acid peptide that regulates nuclear gene expression related to metabolism. In mice fed a high-fat diet, MOTS-c administration improved insulin sensitivity and prevented weight gain.

What the evidence shows

This is primarily animal and in-vitro research. The metabolic effects were demonstrated in mouse models and cell systems. No human clinical trials are included in this study.

What remains uncertain

Whether the metabolic effects observed in mice translate to humans is unknown. Human data on MOTS-c are limited to observational studies showing age-related decline in circulating levels. No controlled human trials have been published.