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首页> 外文期刊>Molecular and Cellular Biology >Mitochondrial Regulation of Cell Death: Mitochondria Are Essential for Procaspase 3-p21 Complex Formation To Resist Fas-Mediated Cell Death
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Mitochondrial Regulation of Cell Death: Mitochondria Are Essential for Procaspase 3-p21 Complex Formation To Resist Fas-Mediated Cell Death

机译：细胞死亡的线粒体调控：线粒体对于Procaspase 3-p21复合物形成抵抗Fas介导的细胞死亡至关重要

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Death receptor Fas transduces cell death signaling upon stimulation by Fas ligand, and this death signaling is mediated by caspase. Recently, we reported that the cell cycle regulator p21 interacts with procaspase 3 to resist Fas-mediated cell death. In the present study, the molecular characterization and functional region of the procaspase 3-p21 complex was further investigated. We observed the p21 expression in the mitochondrial fraction of HepG2 cells and detected Fas-mediated cell death only in the presence of actinomycin D. However, mitochondrial-DNA-lacking HepG2 (MDLH) cells showed this effect even in the absence of actinomycin D. Both p21 and procaspase 3 were expressed in MDLH cells, but the procaspase 3-p21 complex formation was not observed. Interestingly, the resistance to Fas-mediated cell death in the MDLH cells without actinomycin D was recovered after microinjection of HepG2-derived mitochondria into the MDLH cells. We conclude that mitochondria are necessary for procaspase 3-p21 complex formation and propose that the mitochondrial role during cell death is not only death induction but also death suppression.
机译：死亡受体Fas在Fas配体刺激下转导细胞死亡信号，而该死亡信号由caspase介导。最近，我们报道了细胞周期调节因子p21与procaspase 3相互作用来抵抗Fas介导的细胞死亡。在本研究中，进一步研究了procaspase 3-p21复合物的分子表征和功能区域。我们观察到p21在HepG2细胞的线粒体部分中的表达，并且仅在放线菌素D存在的情况下才检测到Fas介导的细胞死亡。但是，即使缺乏放线菌素D，缺少线粒体DNA的HepG2（MDLH）细胞也显示出这种作用。 p21和procaspase 3都在MDLH细胞中表达，但是未观察到procaspase 3-p21复合物的形成。有趣的是，在无放线菌素D的MDLH细胞中，对Fas介导的细胞死亡的抗性在将HepG2衍生的线粒体显微注射到MDLH细胞后得以恢复。我们得出结论，线粒体对于procaspase 3-p21复合物的形成是必需的，并提出线粒体在细胞死亡过程中的作用不仅是死亡诱导，而且是死亡抑制。

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