title: Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks.
abstract: Reprogramming of metabolic pathways contributes to human disease, especially cancer, but the regulators of this process are unknown. Here, we have generated a mouse knockout for the mitochondrial chaperone TRAP-1, a regulator of bioenergetics in tumors. TRAP-1(-/-) mice are viable and showed reduced incidence of age-associated pathologies, including obesity, inflammatory tissue degeneration, dysplasia, and spontaneous tumor formation. This was accompanied by global upregulation of oxidative phosphorylation and glycolysis transcriptomes, causing deregulated mitochondrial respiration, oxidative stress, impaired cell proliferation, and a switch to glycolytic metabolism in vivo. These data identify TRAP-1 as a central regulator of mitochondrial bioenergetics, and this pathway could contribute to metabolic rewiring in tumors.
authors.affiliation: Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA; Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Sofia
authors.initials: S
authors.lastname: Lisanti
authors.affiliation: Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA; Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Tavecchio
authors.affiliation: Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA; Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Young Chan
authors.initials: YC
authors.lastname: Chae
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Angela K
authors.initials: AK
authors.lastname: Brice
authors.affiliation: Department of Radiology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Madhukar L
authors.initials: ML
authors.lastname: Thakur
authors.affiliation: Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA; Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Lucia R
authors.initials: LR
authors.lastname: Languino
authors.affiliation: Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA; Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: daltieri@wistar.org.
authors.forename: Dario C
authors.initials: DC
authors.lastname: Altieri
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D004249:DNA Damage; D017353:Gene Deletion; D006019:Glycolysis; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000235:genetics; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D059467:Transcriptome
chemical_list: D018841:HSP90 Heat-Shock Proteins; C547760:TRAP-1 protein, mouse
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