title: Overexpression of tumor necrosis factor receptor-associated protein 1 (TRAP1), leads to mitochondrial aberrations in mouse fibroblast NIH/3T3 cells.
abstract: Cancer cells undergo uncontrolled proliferation, and aberrant mitochondrial alterations. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein. TRAP1 mRNA is highly expressed in some cancer cell lines and tumor tissues. However, the effects of its overexpression on mitochondria are unclear. In this study, we assessed mitochondrial changes accompanying TRAP1 overexpression, in a mouse cell line, NIH/3T3. We found that overexpression of TRAP1 leads to a series of mitochondrial aberrations, including increase in basal ROS levels, and decrease in mitochondrial biogenesis, together with a decrease in peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) mRNA levels. We also observed increased extracellular signal-regulated kinase (ERK) phosphorylation, and enhanced proliferation of TRAP1 overexpressing cells. This study suggests that overexpression of TRAP1 might be a critical link between mitochondrial disturbances and carcinogenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine; ILCHUN Molecular Medicine Institute MRC, Seoul 110-799; Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul 137-701, Korea.
authors.forename: Chang-Nim
authors.initials: CN
authors.lastname: Im
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine; ILCHUN Molecular Medicine Institute MRC, Seoul 110-799, Korea.
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D020935:MAP Kinase Signaling System; D051379:Mice; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D041681:NIH 3T3 Cells; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
chemical_list: D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C547760:TRAP-1 protein, mouse; C092306:TRAP1 protein, human; D014157:Transcription Factors