HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia
Abstract The mitochondrial paralog of the Hsp90 chaperone family TRAP1 is often induced in tumors, but the mechanisms controlling its expression, as well as its physiological functions remain poorly understood. Here, we find that TRAP1 is highly expressed in the early stages of Zebrafish development...
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2021-05-01
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Series: | Cell Death and Disease |
Online Access: | https://doi.org/10.1038/s41419-021-03716-6 |
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doaj-8e6dec8899704ed197fe94fdfa0442d02021-05-02T11:05:27ZengNature Publishing GroupCell Death and Disease2041-48892021-05-0112511410.1038/s41419-021-03716-6HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxiaClaudio Laquatra0Carlos Sanchez-Martin1Alberto Dinarello2Giuseppe Cannino3Giovanni Minervini4Elisabetta Moroni5Marco Schiavone6Silvio Tosatto7Francesco Argenton8Giorgio Colombo9Paolo Bernardi10Ionica Masgras11Andrea Rasola12Dipartimento di Scienze Biomediche, Università di PadovaDipartimento di Scienze Biomediche, Università di PadovaDipartimento di Biologia, Università di PadovaDipartimento di Scienze Biomediche, Università di PadovaDipartimento di Scienze Biomediche, Università di PadovaIstituto di Scienze e Tecnologie Chimiche, CNRDipartimento di Scienze Biomediche, Università di PadovaDipartimento di Scienze Biomediche, Università di PadovaDipartimento di Biologia, Università di PadovaIstituto di Scienze e Tecnologie Chimiche, CNRDipartimento di Scienze Biomediche, Università di PadovaDipartimento di Scienze Biomediche, Università di PadovaDipartimento di Scienze Biomediche, Università di PadovaAbstract The mitochondrial paralog of the Hsp90 chaperone family TRAP1 is often induced in tumors, but the mechanisms controlling its expression, as well as its physiological functions remain poorly understood. Here, we find that TRAP1 is highly expressed in the early stages of Zebrafish development, and its ablation delays embryogenesis while increasing mitochondrial respiration of fish larvae. TRAP1 expression is enhanced by hypoxic conditions both in developing embryos and in cancer models of Zebrafish and mammals. The TRAP1 promoter contains evolutionary conserved hypoxic responsive elements, and HIF1α stabilization increases TRAP1 levels. TRAP1 inhibition by selective compounds or by genetic knock-out maintains a high level of respiration in Zebrafish embryos after exposure to hypoxia. Our data identify TRAP1 as a primary regulator of mitochondrial bioenergetics in highly proliferating cells following reduction in oxygen tension and HIF1α stabilization.https://doi.org/10.1038/s41419-021-03716-6 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Claudio Laquatra Carlos Sanchez-Martin Alberto Dinarello Giuseppe Cannino Giovanni Minervini Elisabetta Moroni Marco Schiavone Silvio Tosatto Francesco Argenton Giorgio Colombo Paolo Bernardi Ionica Masgras Andrea Rasola |
spellingShingle |
Claudio Laquatra Carlos Sanchez-Martin Alberto Dinarello Giuseppe Cannino Giovanni Minervini Elisabetta Moroni Marco Schiavone Silvio Tosatto Francesco Argenton Giorgio Colombo Paolo Bernardi Ionica Masgras Andrea Rasola HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia Cell Death and Disease |
author_facet |
Claudio Laquatra Carlos Sanchez-Martin Alberto Dinarello Giuseppe Cannino Giovanni Minervini Elisabetta Moroni Marco Schiavone Silvio Tosatto Francesco Argenton Giorgio Colombo Paolo Bernardi Ionica Masgras Andrea Rasola |
author_sort |
Claudio Laquatra |
title |
HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia |
title_short |
HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia |
title_full |
HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia |
title_fullStr |
HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia |
title_full_unstemmed |
HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia |
title_sort |
hif1α-dependent induction of the mitochondrial chaperone trap1 regulates bioenergetic adaptations to hypoxia |
publisher |
Nature Publishing Group |
series |
Cell Death and Disease |
issn |
2041-4889 |
publishDate |
2021-05-01 |
description |
Abstract The mitochondrial paralog of the Hsp90 chaperone family TRAP1 is often induced in tumors, but the mechanisms controlling its expression, as well as its physiological functions remain poorly understood. Here, we find that TRAP1 is highly expressed in the early stages of Zebrafish development, and its ablation delays embryogenesis while increasing mitochondrial respiration of fish larvae. TRAP1 expression is enhanced by hypoxic conditions both in developing embryos and in cancer models of Zebrafish and mammals. The TRAP1 promoter contains evolutionary conserved hypoxic responsive elements, and HIF1α stabilization increases TRAP1 levels. TRAP1 inhibition by selective compounds or by genetic knock-out maintains a high level of respiration in Zebrafish embryos after exposure to hypoxia. Our data identify TRAP1 as a primary regulator of mitochondrial bioenergetics in highly proliferating cells following reduction in oxygen tension and HIF1α stabilization. |
url |
https://doi.org/10.1038/s41419-021-03716-6 |
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