Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks

Research output: Contribution to journalArticle

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.

Details

Authors
  • Sofia Lisanti
  • Michele Tavecchio
  • Young Chan Chae
  • Chang-Qin Liu
  • Angela K Brice
  • Madhukar L Thakur
  • Lucia R Languino
  • Dario C Altieri
External organisations
  • The Wistar Institute
Research areas and keywords

Keywords

  • Aging, Animals, Carcinogenesis, Cell Proliferation, Cellular Reprogramming, DNA Damage, Gene Deletion, Glycolysis, HSP90 Heat-Shock Proteins, Mice, Mice, Inbred C57BL, Mitochondria, Obesity, Oxidative Phosphorylation, Oxidative Stress, Transcriptome
Original languageEnglish
Pages (from-to)671-7
Number of pages7
JournalCell Reports
Volume8
Issue number3
Publication statusPublished - 2014 Aug 7
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes