論文 - 詳細
RRC ID | 53331 |
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著者 | Kamal M, D'Amora DR, Kubiseski TJ. |
タイトル | Loss of hif-1 promotes resistance to the exogenous mitochondrial stressor ethidium bromide in Caenorhabditis elegans. |
ジャーナル | BMC Cell Biol |
Abstract |
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. |
巻・号 | 17 Suppl 1(1) |
ページ | 34 |
公開日 | 2016-9-13 |
DOI | 10.1186/s12860-016-0112-x |
PII | 10.1186/s12860-016-0112-x |
PMID | 27618966 |
PMC | PMC5020483 |
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* |
IF | 3.066 |
引用数 | 2 |
リソース情報 | |
線虫 | tm918 |