MOTS-c Peptide Research Guide

A concise, sourced overview of MOTS-c, a mitochondrial-derived peptide.

Last reviewed and updated:

What is MOTS-c?

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA gene.[1] Unlike most peptides, it is encoded in mitochondrial rather than nuclear DNA. It belongs to a small group of mitochondrial-derived peptides that also includes Humanin.[5]

How was MOTS-c discovered?

MOTS-c was reported in 2015 by Lee and colleagues, who identified it in a screen of short open reading frames within mitochondrial DNA and studied its metabolic effects in cells and mice.[1] In 2018 the same group reported that it can move to the nucleus under metabolic stress.[2]

What is the MOTS-c sequence?

The reported sequence is MRWQEMGYIFYPRKLR, and its calculated molecular weight is roughly 2,174 daltons.[1] More detail is on the FAQ and in the glossary.

What does MOTS-c do in research?

In research models, MOTS-c has been investigated in relation to glucose and insulin handling, AMPK-associated signaling, and nuclear gene regulation during stress.[1][2] These are mechanistic hypotheses from preclinical work, not established effects in people. See the studies database.

Human, animal and cellular evidence

  • Cellular Nuclear translocation and gene-expression changes under metabolic stress.[2]
  • Animal Mouse studies of diet-induced obesity, insulin resistance and age-related physical decline.[1][3]
  • Human Measurements of endogenous MOTS-c around exercise and a genetic association study.[3][4] Details on the human research page.

Current limitations

Published work is dominated by a small number of research groups, and most findings are preclinical. Measuring natural MOTS-c in people does not show what an administered peptide would do. Interpret results cautiously and consult the primary references.