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

Lisanti, Sofia; Tavecchio, Michele LU ; Chae, Young Chan; Liu, Chang-Qin; Brice, Angela K; Thakur, Madhukar L; Languino, Lucia R and Altieri, Dario C (2014) In Cell Reports 8(3). p.7-671
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... (More)

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.

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Contribution to journal
publication status
published
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
in
Cell Reports
volume
8
issue
3
pages
7 pages
publisher
Cell Press
external identifiers
  • scopus:84924602116
ISSN
2211-1247
DOI
10.1016/j.celrep.2014.06.061
language
English
LU publication?
no
id
7dcca3af-e7b7-4ff5-807d-e702185cf8b5
date added to LUP
2017-03-07 09:06:10
date last changed
2017-09-03 05:19:59
@article{7dcca3af-e7b7-4ff5-807d-e702185cf8b5,
  abstract     = {<p>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.</p>},
  author       = {Lisanti, Sofia and Tavecchio, Michele and Chae, Young Chan and Liu, Chang-Qin and Brice, Angela K and Thakur, Madhukar L and Languino, Lucia R and Altieri, Dario C},
  issn         = {2211-1247},
  keyword      = {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},
  language     = {eng},
  month        = {08},
  number       = {3},
  pages        = {7--671},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks},
  url          = {http://dx.doi.org/10.1016/j.celrep.2014.06.061},
  volume       = {8},
  year         = {2014},
}