Peroxiredoxin 3 has a crucial role in the contractile function of skeletal muscle by regulating mitochondrial homeostasis

Kwang Pyo Lee, Yeo Jin Shin, Sung Chun Cho, Seung Min Lee, Young Jae Bahn, Ji Young Kim, Eun Soo Kwon, Do Yeun Jeong, Sang Chul Park, Sue Goo Rhee, Hyun Ae Woo, Ki Sun Kwon

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Antioxidant systems against reactive oxygen species (ROS) are important factors in regulating homeostasis in various cells, tissues, and organs. Although ROS are known to cause to muscular disorders, the effects of mitochondrial ROS in muscle physiology have not been fully understood. Here, we investigated the effects of ROS on muscle mass and function using mice deficient in peroxiredoxin 3 (Prx3), which is a mitochondrial antioxidant protein. Ablation of Prx3 deregulated the mitochondrial network and membrane potential of myotubes, in which ROS levels were increased. We showed that the DNA content of mitochondria and ATP production were also reduced in Prx3-KO muscle. Of note, the mitofusin 1 and 2 protein levels decreased in Prx3-KO muscle, a biochemical evidence of impaired mitochondrial fusion. Contractile dysfunction was examined by measuring isometric forces of isolated extensor digitorum longus (EDL) and soleus muscles. Maximum absolute forces in both the EDL and the soleus muscles were not significantly affected in Prx3-KO mice. However, fatigue trials revealed that the decrease in relative force was greater and more rapid in soleus from Prx3-KO compared to wild-type mice. Taken together, these results suggest that Prx3 plays a crucial role in mitochondrial homeostasis and thereby controls the contractile functions of skeletal muscle.

Original languageEnglish
Pages (from-to)298-306
Number of pages9
JournalFree Radical Biology and Medicine
Volume77
DOIs
StatePublished - 1 Dec 2014

Keywords

  • Fatigue
  • Free radicals
  • Mitochondria
  • Mitofusin
  • Myoblast
  • Myogenesis
  • Oxidative stress
  • Peroxiredoxin 3
  • Reactive oxygen species
  • Skeletal muscle

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