Title |
Loss of hif-1 promotes resistance to the exogenous mitochondrial stressor ethidium bromide in Caenorhabditis elegans
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Published in |
BMC Molecular and Cell Biology, September 2016
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DOI | 10.1186/s12860-016-0112-x |
Pubmed ID | |
Authors |
Muntasir Kamal, Dayana R. D’Amora, Terrance J. Kubiseski |
Abstract |
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. 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. 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. |
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Demographic breakdown
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
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Demographic breakdown
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Student > Ph. D. Student | 5 | 26% |
Student > Doctoral Student | 3 | 16% |
Student > Bachelor | 2 | 11% |
Researcher | 2 | 11% |
Professor | 1 | 5% |
Other | 3 | 16% |
Unknown | 3 | 16% |
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Immunology and Microbiology | 1 | 5% |
Other | 0 | 0% |
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