Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS production in the absence of cytochrome c and AIF release

Roué, Gaël; Bitton, Natacha; Yuste, Vı́ctor J.; Montange, Thomas; Rubio, Manuel; Dessauge, Frédéric; Delettre, Cécile; Merle-Béral, Hélène; Sarfati, Marika; Susin, Santos A.

doi:10.1016/s0300-9084(03)00129-9

Cited by 45 publications

(40 citation statements)

References 19 publications

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“…Thus, as in the case of type II PCD, 3-MA seems to Letters to the Editor regulate type III cell death at an early stage, upstream of the mitochondrial damage characterizing this kind of death. 5,7 Altogether, this part of our study provides a first time evidence of a crosstalk between type II and type III PCD. Importantly, the identification of new modulators of type III PCD, such as 3-MA, might pave the way for novel pharmacological strategies against the pathological PCD characterizing CLL.…”

supporting

confidence: 61%

Caspase-independent type III PCD: a new means to modulate cell death in chronic lymphocytic leukemia

et al. 2008

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supporting

confidence: 61%

Caspase-independent type III PCD: a new means to modulate cell death in chronic lymphocytic leukemia

et al. 2008

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“…Interestingly, caspase-independent cell death has also been described for two other mAb-activated cell surface molecules, CD47 and CD99, in leukemic cells. However, CD47-and CD99-induced cell death differs from CD44-induced HEL cell death as it occurs very rapidly after antigen ligation, involves an early reorganization of cytoskeleton and is AIF-independent (Mateo et al, 2002;Roue et al, 2003;Cerisano et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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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“…Oligonucleosomal DNA fragmentation was detected by agarose gel electrophoresis as described elsewhere (65).…”

Section: Methodsmentioning

confidence: 99%

Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells

Bras

Yuste

Roué

et al. 2007

Molecular and Cellular Biology

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116

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Ligation of CD47 triggers caspase-independent programmed cell death (PCD) in normal and leukemic cells. Here, we characterize the morphological and biochemical features of this type of death and show that it displays the hallmarks of type III PCD. A molecular and biochemical approach has led us to identify a key mediator of this type of death, dynamin-related protein 1 (Drp1). CD47 ligation induces Drp1 translocation from cytosol to mitochondria, a process controlled by chymotrypsin-like serine proteases. Once in mitochondria, Drp1 provokes an impairment of the mitochondrial electron transport chain, which results in dissipation of mitochondrial transmembrane potential, reactive oxygen species generation, and a drop in ATP levels. Surprisingly, neither the activation of the most representative proapoptotic members of the Bcl-2 family, such as Bax or Bak, nor the release of apoptogenic proteins AIF (apoptosis-inducing factor), cytochrome c, endonuclease G (EndoG), Omi/HtrA2, or Smac/DIABLO from mitochondria to cytosol is observed. Responsiveness of cells to CD47 ligation increases following Drp1 overexpression, while Drp1 downregulation confers resistance to CD47-mediated death. Importantly, in B-cell chronic lymphocytic leukemia cells, mRNA levels of Drp1 strongly correlate with death sensitivity. Thus, this previously unknown mechanism controlling caspase-independent type III PCD may provide the basis for novel therapeutic approaches to overcome apoptotic avoidance in malignant cells.

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Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS production in the absence of cytochrome c and AIF release

Cited by 45 publications

References 19 publications

Caspase-independent type III PCD: a new means to modulate cell death in chronic lymphocytic leukemia

Caspase-independent type III PCD: a new means to modulate cell death in chronic lymphocytic leukemia

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

Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells

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