title: Peroxiredoxin 3 has a crucial role in the contractile function of skeletal muscle by regulating mitochondrial homeostasis.
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.
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Kwang-Pyo
authors.initials: KP
authors.lastname: Lee
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, Daejeon 305-333, Republic of Korea.
authors.forename: Yeo Jin
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: Well Aging Research Center, Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd, Gyeonggi-do 446-712, Republic of Korea.
authors.forename: Sung Chun
authors.initials: SC
authors.lastname: Cho
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Bahn
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Eun-Soo
authors.initials: ES
authors.lastname: Kwon
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, Daejeon 305-333, Republic of Korea.
authors.forename: Do Yeun
authors.initials: DY
authors.lastname: Jeong
authors.affiliation: Well Aging Research Center, Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd, Gyeonggi-do 446-712, Republic of Korea.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
authors.affiliation: Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Women׳s University, Seoul 120-750, Republic of Korea.
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Department of Functional Genomics, Korea University of Science and Technology, Daejeon 305-333, Republic of Korea. Electronic address: kwonks@kribb.re.kr.
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Kwon
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology*; D006706:Homeostasis; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D018398:Homeodomain Proteins; D017382:Reactive Oxygen Species; C484663:Shox2 protein, mouse; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse
keywords: Fatigue; Free radicals; Mitochondria; Mitofusin; Myoblast; Myogenesis; Oxidative stress; Peroxiredoxin 3; Reactive oxygen species; Skeletal muscle