Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)

Diabetes Metab J. 2022 May;46(3):402-413. doi: 10.4093/dmj.2022.0092. Epub 2022 May 25.

Abstract

Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPRmt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.

Keywords: Exercise; Hormesis; MOTS-c peptide, human; Mitochondria; Mitochondrial proteins; Obesity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exercise
  • Mitochondria*
  • RNA, Ribosomal*
  • Transcription Factors

Substances

  • RNA, Ribosomal
  • RNA, ribosomal, 12S
  • Transcription Factors