MOTS-c

MOTS-c is a peptide of just 16 amino acids with an unusual origin: its instructions sit in the DNA inside mitochondria, the parts of the cell that generate energy, rather than in the cell's main nuclear DNA. Researchers call this kind of molecule a mitochondrial-derived peptide, and study it as a hormone-like signal sent out by mitochondria that may influence metabolism, exercise physiology and aging related pathways.

What it is

MOTS-c appears to function as a mitohormone, sending hormone-like signals from mitochondria rather than from a gland. Under metabolic stress, it can travel into the cell nucleus and influence which genes are switched on, mainly through a chain of signals called the folate-AICAR-AMPK pathway, a route also touched by exercise and by some diabetes medicines.

Because MOTS-c is encoded in mitochondrial rather than nuclear DNA, researchers treat it as a distinct signaling molecule worth studying on its own, separate from peptide hormones made through the cell's usual nuclear gene machinery.

How it is studied

Research on MOTS-c is mainly in mice, including pregnant mice used as a model for pregnancy-related high blood sugar, and mice given a single injection before running to measure exercise performance. The available human data comes from measuring the peptide's natural level in blood or muscle rather than from giving it to people directly.

What studies report

A mouse study of pregnancy-related high blood sugar reported that MOTS-c reduced high blood sugar and improved insulin sensitivity in pregnant mice, and separately found that women with the same condition had lower natural blood levels of MOTS-c than women without it. [1]
A study in untrained mice reported that one injection improved running time by 12 percent and running distance by 15 percent, and that regular training on its own raised natural MOTS-c protein in muscle tissue by one and a half to five fold. [2]
A study across mice of different ages, together with human muscle samples, reported that MOTS-c supported physical performance at every age tested in mice, and that a single bout of exercise raised natural MOTS-c levels in human muscle by nearly twelve fold. [3]

What is not known

Most of the performance and metabolic findings described here come from mice rather than people, and the human data cited measures the body's own natural MOTS-c levels rather than testing an amount given to a person from outside. Whether giving MOTS-c directly to people would reproduce the mouse findings has not been established in the citations reviewed here.

Regulatory status

MOTS-c is not approved by the United States Food and Drug Administration for any human use. The World Anti-Doping Agency also names it on its list of prohibited substances for competitive athletes, citing its capacity to activate the AMPK metabolic pathway.