title: Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis.
abstract: Tid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear.
  
  
  
  In vitro induced differentiation assay of mouse myoblast C2C12 cells was applied to examine the physiological role of Tid1 during skeletal myogenesis. In addition, transgenic mice with muscle specific (HSA-Cre) Tid1 deletion were established and examined to determine the physiological function of Tid1 during skeletal muscle development in vivo.
  
  
  
  Expression of Tid1 protein was upregulated in the differentiated C2C12 cells, and the HSA-Tid1f/fmice displayed muscular dystrophic phenotype. The expression of myosin heavy chain (MyHC), the protein served as the muscular development marker, was reduced in HSA-Tid1f/fmice at postnatal day (P)5 and P8. The protein levels of ATP sensor (p-AMPK) and mitochondrial biogenesis protein (PGC-1α) were also significantly reduced in HSA-Tid1f/fmice. Moreover, Tid1 deficiency induced apoptotic marker Caspase-3 in muscle tissues of HSA-Tid1f/fmice. Consistent with the in vivo finding, we observed that downregulation of Tid1 not only reduced the ATP production but also abolished the differentiation ability of C2C12 cells by impairing the mitochondrial activity.
  
  
  
  Together, our results suggest that Tid1 deficiency reduces ATP production and abolishes mitochondrial activity, resulting in energy imbalance and promoting apoptosis of muscle cells during myogenesis. It will be of importance to understand the function of Tid1 during human muscular dystrophy in the future.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Li-Hao
authors.initials: LH
authors.lastname: Cheng
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Hung
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Chinese Medical Science and Institute of Medical Science, China Medical University, Taichung, Taiwan, Republic of China.|Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, Republic of China.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Chiu
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China. jflo@ym.edu.tw.|Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan, Republic of China. jflo@ym.edu.tw.|Graduate Institute of Chinese Medical Science and Institute of Medical Science, China Medical University, Taichung, Taiwan, Republic of China. jflo@ym.edu.tw.|Department of Dentistry, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. jflo@ym.edu.tw.|Genome Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China. jflo@ym.edu.tw.|National Yang-Ming University VGH Genome Research Center, Taipei, Taiwan, Republic of China. jflo@ym.edu.tw.
authors.forename: Jeng-Fan
authors.identifier: 0000-0001-7188-9140
authors.initials: JF
authors.lastname: Lo
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. huangtf@vghtpe.gov.tw.|Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China. huangtf@vghtpe.gov.tw.
authors.forename: Tung-Fu
authors.initials: TF
authors.lastname: Huang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004734:Energy Metabolism / Q000502:physiology*; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D009136:Muscular Dystrophies / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism
chemical_list: C485636:Dnaja3 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D053148:Caspase 3; D018995:Myosin Heavy Chains
keywords: AMPK and PGC-1α; ATP; Co-chaperone; Skeletal muscle