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




Loss of hif-1 promotes resistance to the exogenous mitochondrial stressor ethidium bromide in Caenorhabditis elegans - Download this document for free, or read online. Document in PDF available to download.

BMC Cell Biology

, 17:34

Cytoplasmic and organelle biology

Abstract

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.

KeywordsC. elegans DJ-1 Hypoxia inducible factor Mitochondria p38 MAPK AbbreviationsDICDifferential interference contrast

EtBrEthidium bromide

ETCElectron transport chain

H2DCF-DA2′,7′-dihydrochlorofluorescein diacetate

HIF-1Hypoxia inducible factor 1

mtDNAMitochondrial DNA

mtUPRMitochondrial unfolded protein response

PCRPolymerase chain reaction

PDParkinson’s disease

qRT-PCRQuantitative reverse transcriptase polymerase chain reaction

ROSReactive oxygen species

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Author: Muntasir Kamal - Dayana R. D’Amora - Terrance J. Kubiseski

Source: https://link.springer.com/



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