Calpain I Induces Cleavage and Release of Apoptosis-inducing Factor from Isolated Mitochondria

Polster, Brian M.; Basáñez, Gorka; Etxebarria, Aitor; Hardwick, J. Marie; Nicholls, David G.

doi:10.1074/jbc.m413269200

Cited by 395 publications

(335 citation statements)

References 55 publications

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“…Indeed, AIF needs to be cleaved for becoming a soluble and apoptogenic protein (Otera et al, 2005). Recent studies in isolated mitochondria have shown that AIF cleavage is caspase-independent and involves specific cysteine proteases like calpain I or cathepsins B, L and S (Polster et al, 2005;Yuste et al, 2005). Here, we show that calpain inhibition not only decreases A3D8-induced cell death but also inhibits AIF translocation suggesting that AIF release from mitochondria may be a direct consequence of calpain activity in HEL cells.…”

Section: Cd44-induced Cell Death In Erythroleukemia Cellsmentioning

confidence: 48%

“…Finally, and because it has recently reported that calpain I can induce cleavage and release of AIF from isolated mitochondria (Polster et al, 2005), we examined whether calpain inhibition could affect AIF release observed during A3D8-induced cell death. Treatment with the calpain inhibitor calpeptin (Figure 7d) efficiently decreased AIF nuclear translocation in A3D8-treated HEL cells.…”

Section: Cd44-induced Cell Death In Erythroleukemia Cells C Artus Et Almentioning

confidence: 99%

“…Under physiological conditions, AIF is a mitochondrial FAD-dependent oxidoreductase that plays a role in oxidative phosphorylation (Miramar et al, 2001). However, after a cellular insult, AIF is cleaved by calpains and/or cathepsins (Polster et al, 2005;Yuste et al, 2005) and translocates from mitochondria to cytosol and to nucleus where it causes, in a caspase-independent fashion, chromatin condensation and large-scale (B50 kb) DNA fragmentation (Susin et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (DWm), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these effects including cell death, loss of mitochondrial DWm and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline. A significant protection against cell death was also observed by using small interfering RNA for AIF. Moreover, we show that calpain protease was activated before the appearance of apoptosis, and that calpain inhibitors or transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF release. These data suggest that CD44 ligation triggers a novel caspaseindependent cell death pathway via calpain-dependent AIF release in erythroleukemic HEL cells.

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Section: Cd44-induced Cell Death In Erythroleukemia Cellsmentioning

confidence: 48%

Section: Cd44-induced Cell Death In Erythroleukemia Cells C Artus Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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“…Once relocalized to the cytosol, cytochrome c activates caspase-9 by binding its regulatory subunit Apaf-1, a AAA ATPase-related protein with a C-terminal WD repeat protein (Li et al, 1997;Yu et al, 2005). Additional pro-death factors that are released from mitochondria (e.g., AIF, SMAC/Diablo, Omi/Htr2A) were reported to activate both caspase-dependent and caspase-independent death programs, though controversies remain (Foghsgaard and Jaattela, 1997;Jaattela, 2002;Garrido and Kroemer, 2004;Saelens et al, 2004;Polster et al, 2005). This mitochondrial outer membrane permeabilization (MOMP) occurs by an unknown biochemical mechanism that requires one or both of the pro-death multidomain Bcl-2 family proteins Bax and Bak (Hardwick and Polster, 2002;Green and Kroemer, 2004).…”

Section: The Executioner Mitochondrionmentioning

confidence: 99%

Mitochondrial factors with dual roles in death and survival

Berman

Ivanovska

et al. 2006

Oncogene

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At least in mammals, we have some understanding of how caspases facilitate mitochondria-mediated cell death, but the biochemical mechanisms by which other factors promote or inhibit programmed cell death are not understood. Moreover, most of these factors are only studied after treating cells with a death stimulus. A growing body of new evidence suggests that cell death regulators also have 'day jobs' in healthy cells. Even caspases, mitochondrial fission proteins and pro-death Bcl-2 family proteins appear to have normal cellular functions that promote cell survival. Here, we review some of the supporting evidence and stretch beyond the evidence to seek an understanding of the remaining questions.

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“…Indeed, AIF is a flavoprotein that can oxidize NADH and NADPH in vitro (Miramar et al, 2001) and may participate in the detoxification of reactive oxygen species (Klein et al, 2002) and in the maintenance of glutathione levels (Cande et al, 2004b), although the mechanisms of this antioxidant activity remain to be determined. Upon activation of a serine protease that liberates AIF from its membrane attachment (Polster et al, 2005;Yuste et al, 2005), combined with outer mitochondrial membrane permeabilization, for instance through Bax/Bak-mediated pores (Green and Kroemer, 2004), AIF is released from mitochondria and participates in the catastrophic catabolic process that allows the digestion of the cellular content from within.…”

Section: Introductionmentioning

confidence: 99%

Physical interaction of apoptosis-inducing factor with DNA and RNA

et al. 2005

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Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein, which upon apoptosis induction translocates to the nucleus where it interacts with DNA by virtue of positive charges clustered on the AIF surface. Here we show that the AIF interactome, as determined by mass spectroscopy, contains a large panel of ribonucleoproteins, which apparently bind to AIF through the RNA moiety. However, AIF is devoid of any detectable RNAse activity both in vitro and in vivo. Recombinant AIF can directly bind to DNA as well as to RNA. This binding can be visualized by electron microscopy, revealing that AIF can condense DNA, showing a preferential binding to singlestranded over double-stranded DNA. AIF also binds and aggregates single-stranded and structured RNA in vitro. Single-stranded poly A, poly G and poly C, as well doublestranded A/T and G/C RNA competed with DNA for AIF binding with a similar efficiency, thus corroborating a computer-calculated molecular model in which the binding site within AIF is the same for distinct nucleic acid species, without a clear sequence specificity. Among the preferred electron donors and acceptors of AIF, nicotine adenine dinucleotide phosphate (NADP) was particularly efficient in enhancing the generation of higher-order AIF/ DNA and AIF/RNA complexes. Altogether, these data support a model in which a direct interaction of AIF contributes to the compaction of nucleic acids within apoptotic cells.

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Calpain I Induces Cleavage and Release of Apoptosis-inducing Factor from Isolated Mitochondria

Cited by 395 publications

References 55 publications

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

Mitochondrial factors with dual roles in death and survival

Physical interaction of apoptosis-inducing factor with DNA and RNA

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