Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks
(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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- author
- Lisanti, Sofia ; Tavecchio, Michele LU ; Chae, Young Chan ; Liu, Chang-Qin ; Brice, Angela K ; Thakur, Madhukar L ; Languino, Lucia R and Altieri, Dario C
- publishing date
- 2014-08-07
- type
- 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
-
- pmid:25088416
- 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
- 2024-04-14 07:18:01
@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}},
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}},
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}},
doi = {{10.1016/j.celrep.2014.06.061}},
volume = {{8}},
year = {{2014}},
}