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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Sofia Lisanti
  • Michele Tavecchio
  • Young Chan Chae
  • Chang-Qin Liu
  • Angela K Brice
  • Madhukar L Thakur
  • Lucia R Languino
  • Dario C Altieri
Externa organisationer
  • The Wistar Institute
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)671-7
Antal sidor7
TidskriftCell Reports
Volym8
Utgivningsnummer3
StatusPublished - 2014 aug 7
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa