Endurance training enhances skeletal muscle mitochondrial respiration by promoting MOTS-c secretion

Yiwei Feng; Zhijian Rao; Xu Tian; Yi Hu; Liantian Yue; Yifan Meng; Qiuling Zhong; Wei Chen; Wenlong Xu; Haoran Li; Yingjia Hu; Rengfei Shi

doi:10.1016/j.freeradbiomed.2024.12.038

Endurance training enhances skeletal muscle mitochondrial respiration by promoting MOTS-c secretion

Free Radic Biol Med. 2024 Dec 18:S0891-5849(24)01147-X. doi: 10.1016/j.freeradbiomed.2024.12.038. Online ahead of print.

Authors

Yiwei Feng¹, Zhijian Rao², Xu Tian¹, Yi Hu¹, Liantian Yue³, Yifan Meng¹, Qiuling Zhong¹, Wei Chen¹, Wenlong Xu¹, Haoran Li¹, Yingjia Hu¹, Rengfei Shi⁴

Affiliations

¹ School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China.
² School of Physical Education, Shanghai Normal University, Shanghai 200234, China.
³ School of Sport, Exercise and Health Sciences, Loughborough University, Britain.
⁴ School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China. Electronic address: rfshi@sus.edu.cn.

PMID: 39706498
DOI: 10.1016/j.freeradbiomed.2024.12.038

Abstract

The mitochondrial open reading frame of 12S rRNA-c (MOTS-c) is a biologically active mitochondria-derived peptide. However, the relationship between MOTS-c, skeletal muscle mitochondrial function, and endurance exercise adaptations is unknown. Here, we tested indices such as maximal oxygen uptake and serum MOTS-c levels in marathon runners and sedentary subjects. In addition, we tested aerobic exercise capacity, skeletal muscle mitochondrial respiration rate, and serum MOTS-c levels in mice subjected to long-term endurance training groups and sedentary groups. Our results indicated a close association between serum MOTS-c levels and aerobic exercise capacity. Circulating MOTS-c levels are expected to be an important indicator for predicting aerobic exercise capacity and assessing body fat status, endurance training load, and physical function. More importantly, we found that endurance training may enhance the mitochondrial respiratory function of skeletal muscle by promoting the secretion of MOTS-c and activating the AMPK/PGC-1α pathway.

Keywords: exercise; mitochondria; mitochondrial-derived peptides; skeletal muscle; the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c).