PUBLICATION
HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia
- Authors
- Laquatra, C., Sanchez-Martin, C., Dinarello, A., Cannino, G., Minervini, G., Moroni, E., Schiavone, M., Tosatto, S., Argenton, F., Colombo, G., Bernardi, P., Masgras, I., Rasola, A.
- ID
- ZDB-PUB-210504-5
- Date
- 2021
- Source
- Cell Death & Disease 12: 434 (Journal)
- Registered Authors
- Argenton, Francesco, Schiavone, Marco
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Hypoxia
- Disease Models, Animal
- Energy Metabolism/immunology*
- HSP90 Heat-Shock Proteins/metabolism*
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
- Molecular Chaperones/metabolism*
- Zebrafish
- PubMed
- 33934112 Full text @ Cell Death Dis.
Citation
Laquatra, C., Sanchez-Martin, C., Dinarello, A., Cannino, G., Minervini, G., Moroni, E., Schiavone, M., Tosatto, S., Argenton, F., Colombo, G., Bernardi, P., Masgras, I., Rasola, A. (2021) HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia. Cell Death & Disease. 12:434.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping