BNIP3 and Genetic Control of Necrosis-Like Cell Death through the Mitochondrial Permeability Transition Pore

Velde, Christine Vande; Cizeau, Jeannick; Dubik, Don; Alimonti, Judie B.; Brown, Thomas L.; Israels, Sara J.; Hakem, Razqallah; Greenberg, Arnold H.

doi:10.1128/mcb.20.15.5454-5468.2000

Cited by 570 publications

(510 citation statements)

References 66 publications

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“…BNIP3-mediated atypical cell death has also been reported in other cell systems, where cells exhibited nuclear apoptotic change in the absence of Apaf-1, cytochrome c release and caspase activation [40,41]. We have also observed that cyanide can produce apoptosis in rat primary cortical cells in which BNIP3 released cytochrome c from mitochondria, followed by caspase-dependent apoptosis [18].…”

Section: Discussionsupporting

confidence: 76%

“…Forced overexpression of BNIP3 in Mes 23.5 cells decreased ΔΨ m , which was prevented by CsA, an MPT inhibitor. Previous studies have shown that upon overexpression, BNIP3 integrates into the outer mitochondrial membrane with a special orientation of the N-terminus in the cytoplasm and Cterminus in the membrane [41]. After integration into the mitochondrial membrane, BNIP3 may interact with components of the MPT pore to induce rapid opening of the MPT pore to dissipate ΔΨm.…”

Section: Discussionmentioning

confidence: 99%

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HIF-1α activation by a redox-sensitive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial-dependent cell death

Zhang

Liu

et al. 2007

Free Radical Biology and Medicine

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Cyanide produces degeneration of the nervous system in which different modes of cell death are activated in the vulnerable brain areas. In brain, the mechanism underlying the cell death is not clear. In this study, an immortalized dopaminergic cell line was used to characterize the cell death signaling cascade activated by cyanide. Cyanide-treated cells exhibited a time-and concentration-dependent apoptosis that was caspase-independent. Cyanide induced a rapid surge of intracellular reactive oxygen species (ROS) generation, followed by p38 mitogen-activated protein kinase (MAPK) activation and nuclear accumulation of hypoxia-inducible factor-1α (HIF-1α). Activation of p38 MAPK and HIF-1α accumulation were attenuated by N-acetyl-L-cysteine (antioxidant), catalase (hydrogen peroxide scavenger) or a selective p38 MAPK inhibitor (SB203580). Cyanide activated the hypoxia response element (HRE) promoter, which was also blocked by the antioxidants and SB203580. HRE activation was followed by increased BNIP3 gene transcription, as reflected by elevated BNIP3 mRNA and protein levels. BNIP3 upregulation was reduced by selective RNAi knockdown of HIF-1α. Overexpression of BNIP3 produced mitochondrial dysfunction (reduced membrane potential), caspase-independent apoptosis, and sensitization of the cells to cyanideinduced toxicity. Expression of a dominant negative mutant or RNAi knockdown of BNIP3 protected the cells from cyanide. It was concluded that cyanide activated the HIF-1α-mediated pathway of BNIP3 induction through a redox-sensitive process. Increased BNIP3 expression then served as an initiator of mitochondrial-mediated death.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

HIF-1α activation by a redox-sensitive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial-dependent cell death

Zhang

Liu

et al. 2007

Free Radical Biology and Medicine

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“…47 Overexpression of BNIP3 results in a caspaseindependent cell death with features of necrosis, including opening of the permeability transition pore, and evidence of mitochondrial autophagy. 48 Hspin is a transmembrane protein that is localized primarily in the mitochondria. Overexpression of HSpin (the human Spin homologue) also induces a caspase-independent cell death that involves mitochondrial autophagy and is inhibited by Bcl-2 and Bcl-xL.…”

Section: Inhibition Of Apoptosis Upstream Of the Mitochondria Preventmentioning

confidence: 99%

Macroautophagy versus mitochondrial autophagy: a question of fate?

Kundu

Thompson²

2005

Cell Death Differ

107

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Autophagy is a catabolic process that allows recycling of cytoplasmic components (including organelles) into basic components, offering a bioenergetically efficient alternative to de novo synthesis. In yeast, autophagy functions primarily as an adaptive mechanism allowing survival in the response to changes in the availability of nutrients in the environment. Over the past decade, genetic screens performed in yeast have elucidated many of the molecular components involved in this adaptive response. [1][2][3] More recently, the roles of homologous genes are being explored in multicellular organisms and in cells derived from these organisms. 4 These studies have demonstrated that while autophagy is often induced as part of an adaptive response, induction of autophagy may also lead to cell death. During Drosophila larval development, for example, starvation-induced autophagy occurs in the larval fat body and is required for maintaining circulating nutrient levels and survival of the larvae under unfavorable nutritional conditions; 5 by contrast, programmed autophagy results in cell death and is the primary means of removing certain larval organs during metamorphosis. 6 On a cellular level, autophagy is observed prior to apoptosis in growth factor-deprived neuronal cultures. 7,8 In cells lacking critical proapoptotic proteins, the adaptive process of autophagy aimed at maintaining bioenergetic homeostasis can be unmasked in response to growthfactor withdrawal. 9 In contrast, cell death in response to a variety of chemicals has been suggested to result from autophagic destruction of the cell and to be suppressed by inhibition of autophagy. 10 The factors that determine whether induction of autophagy contributes to cell survival or cell death are not well-elucidated; however, two key issues may be the rate of autophagic degradation and the specificity of the engulfed components. Although autophagy is generally considered a nonspecific process, there are instances where the mitochondria (and other organelles) appear to be specifically targeted. Here, we focus on the signals and pathways involved in regulating the induction of autophagy and mitochondrial autophagy in yeast and how these processes are relevant to survival and death of mammalian cells.In general terms, 'autophagy' refers to any intracellular process that involves the degradation of cytosolic components by the lysosome. There are at least three distinct autophagic pathways: macroautophagy, microautophagy and chaperone-mediated autophagy. Macroautophagy is a multistep process by which portions of cytoplasm and/or organelles are sequestered in a double or multimembrane structure ('autophagosome') and delivered to the lysosome for degradation (Figure 1). Upon fusion of the autophagosome with the lysosome, it becomes an autophagolysosome or autophagic vacuole. Although macroautophagy is generally considered a nonspecific process there are instances in which organelles, such as mitochondria and peroxisomes, appear to be preferentially sequestered. These process...

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confidence: 99%

“…Forced expression of BNIP3 induces cell death characterised by localisation of the protein at the mitochondria, opening of the permeability transition pore, loss of membrane potential and production of reactive oxygen species (Regula et al, 2002;Vande Velde et al, 2000). This form of cell death is independent of cytochrome c release from mitochondria and caspase activation (Vande Velde et al, 2000). Expression of BNIP3, which is dramatically increased in response to hypoxia, is regulated in part by hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor comprised of an oxygenregulated a subunit (HIF-1a) and a stale nuclear factor (HIF-1b/ ARNT), and known to be a mediator of the hypoxic response (Semenza, 1999).…”

mentioning

confidence: 99%

Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours

et al. 2005

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Hypoxia is a key factor contributing to the progression of human neoplasias and to the development of resistance to chemotherapy. BNIP3 is a proapoptotic member of the Bcl-2 protein family involved in hypoxia-induced cell death. We evaluated the expression and methylation status of BNIP3 gene to better understand the role of epigenetic alteration of its expression in haematopoietic tumours. Methylation of the region around the BNIP3 transcription start site was detected in four acute lymphocytic leukaemia, one multiple myeloma and one Burkitt lymphoma cell lines, and was closely associated with silencing the gene. That expression of BNIP3 was restored by treatment with 5-aza2 0 -deoxycytidine (5-aza-dC), a methyltransferase inhibitor, which confirmed the gene to be epigenetically inactivated by methylation. Notably, re-expression of BNIP3 using 5-aza2-dC also restored hypoxia-mediated cell death in methylated cell lines. Acetylation of histone H3 in the 5 0 region of the gene, which was assessed using chromatin immunoprecipitation assays, correlated directly with gene expression and inversely with DNA methylation. Among primary tumours, methylation of BNIP3 was detected in five of 34 (15%) acute lymphocytic leukaemias, six of 35 (17%) acute myelogenous leukaemias and three of 14 (21%) multiple myelomas. These results suggest that aberrant DNA methylation of the 5 0 CpG island and histone deacetylation play key roles in silencing BNIP3 expression in haematopoietic tumours.

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BNIP3 and Genetic Control of Necrosis-Like Cell Death through the Mitochondrial Permeability Transition Pore

Cited by 570 publications

References 66 publications

HIF-1α activation by a redox-sensitive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial-dependent cell death

HIF-1α activation by a redox-sensitive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial-dependent cell death

Macroautophagy versus mitochondrial autophagy: a question of fate?

Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours

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