The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase

We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory down...

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Autores principales: Sciacovelli, Marco, Guzzo, Giulia, Morello, Virginia, Frezza, Christian, Zheng, Liang, Nannini, Nazarena, Calabrese, Fiorella, Laudiero, Gabriella, Esposito, Franca, Landriscina, Matteo, Defilippi, Paola, Bernardi, Paolo, Rasola, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2013
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677096/
https://www.ncbi.nlm.nih.gov/pubmed/23747254
http://dx.doi.org/10.1016/j.cmet.2013.04.019
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author Sciacovelli, Marco
Guzzo, Giulia
Morello, Virginia
Frezza, Christian
Zheng, Liang
Nannini, Nazarena
Calabrese, Fiorella
Laudiero, Gabriella
Esposito, Franca
Landriscina, Matteo
Defilippi, Paola
Bernardi, Paolo
Rasola, Andrea
author_facet Sciacovelli, Marco
Guzzo, Giulia
Morello, Virginia
Frezza, Christian
Zheng, Liang
Nannini, Nazarena
Calabrese, Fiorella
Laudiero, Gabriella
Esposito, Franca
Landriscina, Matteo
Defilippi, Paola
Bernardi, Paolo
Rasola, Andrea
author_sort Sciacovelli, Marco
collection PubMed
description We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target.
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spelling pubmed-36770962013-06-10 The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase Sciacovelli, Marco Guzzo, Giulia Morello, Virginia Frezza, Christian Zheng, Liang Nannini, Nazarena Calabrese, Fiorella Laudiero, Gabriella Esposito, Franca Landriscina, Matteo Defilippi, Paola Bernardi, Paolo Rasola, Andrea Cell Metab Article We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target. Cell Press 2013-06-04 /pmc/articles/PMC3677096/ /pubmed/23747254 http://dx.doi.org/10.1016/j.cmet.2013.04.019 Text en © 2013 ELL & Excerpta Medica. This document may be redistributed and reused, subject to certain conditions (http://www.elsevier.com/wps/find/authorsview.authors/supplementalterms1.0) .
spellingShingle Article
Sciacovelli, Marco
Guzzo, Giulia
Morello, Virginia
Frezza, Christian
Zheng, Liang
Nannini, Nazarena
Calabrese, Fiorella
Laudiero, Gabriella
Esposito, Franca
Landriscina, Matteo
Defilippi, Paola
Bernardi, Paolo
Rasola, Andrea
The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
title The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
title_full The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
title_fullStr The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
title_full_unstemmed The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
title_short The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
title_sort mitochondrial chaperone trap1 promotes neoplastic growth by inhibiting succinate dehydrogenase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677096/
https://www.ncbi.nlm.nih.gov/pubmed/23747254
http://dx.doi.org/10.1016/j.cmet.2013.04.019
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