Loss of hif-1 promotes resistance to the exogenous mitochondrial stressor ethidium bromide in Caenorhabditis elegans

BMC Cell Biology

Research Article

Dayana R. D’Amora¹  Terrance J. Kubiseski²  Muntasir Kamal³ 

[1] Department of Biology, York University, Toronto, Canada;Department of Biology, York University, Toronto, Canada;Department of Neuroscience, York University, Toronto, Canada;Department of Biology, York University, Toronto, Canada;Present address: Department of Molecular Genetics, University of Toronto, Toronto, Canada;

关键词: C. elegans;    DJ-1;    Hypoxia inducible factor;    Mitochondria;    p38 MAPK;   

DOI  :  10.1186/s12860-016-0112-x

 received in 2015-12-16, accepted in 2016-09-06,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMitochondrial dysfunction is one of the leading causes of neurological disorders in humans. Mitochondrial perturbations lead to adaptive mechanisms that include HIF-1 stabilization, though the consequences of increased levels of HIF-1 following mitochondrial stress remain poorly understood.ResultsUsing Caenorhabditis elegans, we show that a hif-1 loss-of-function mutation confers resistance towards the mitochondrial toxin ethidium bromide (EtBr) and suppresses EtBr-induced production of ROS. In mammals, the PD-related gene DJ-1 is known to act as a redox sensor to confer protection against antioxidants and mitochondrial inhibitors. A deletion mutant of the C. elegans homolog djr-1.1 also showed increased resistance to EtBr. Furthermore, our data implicates p38 MAP kinase as an indispensable factor for survival against mitochondrial stress in both hif-1 and djr-1.1 mutants. ConclusionsWe propose that EtBr-induced HIF-1 activates pathways that are antagonistic in conferring protection against EtBr toxicity and that blocking HIF-1 activity may promote survival in cells with compromised mitochondrial function.

【 授权许可】

CC BY   
© The Author(s). 2016