Reference - Detail
|Author||Kamal M, D'Amora DR, Kubiseski TJ.|
|Title||Loss of hif-1 promotes resistance to the exogenous mitochondrial stressor ethidium bromide in Caenorhabditis elegans.|
|Journal||BMC Cell Biol.|
BACKGROUND:Mitochondrial 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.
RESULTS:Using 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.
CONCLUSIONS:We 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.
|Volume||17 Suppl 1|
|MeSH||Aldehyde Oxidoreductases / metabolism Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Ethidium / pharmacology* Hypoxia-Inducible Factor 1 / metabolism* Mitochondria / drug effects Mitochondria / metabolism* Mutation / genetics Reactive Oxygen Species / metabolism Transcription Factors / metabolism*|