BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis.

BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis.
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DOI:
10.1007/s10495-020-01627-z
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发表时间:
2020-10
期刊:
Apoptosis : an international journal on programmed cell death
影响因子:
--
通讯作者:
Lee YJ
Lee YJ
中科院分区:
其他
文献类型:
--
作者:
Lee YS;Kalimuthu K;Park YS;Luo X;Choudry MHA;Bartlett DL;Lee YJ

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与其他类型的死亡如细胞凋亡相比,铁凋亡被认为是一种独特的细胞死亡形式。已知它是由铁依赖性的脂质过氧化物积累而不是半胱天冬酶激活引起的。然而,我们最近报道,铁凋亡与细胞凋亡相互作用。在这项研究中,我们研究了一种可能的机制,这种相互作用之间的铁凋亡和细胞凋亡。我们的研究结果表明,铁促凋亡剂erastin和凋亡剂TRAIL的联合治疗有效地破坏了线粒体膜电位(Δ Vm),随后促进了caspase的激活。线粒体膜电位的改变可能是由于在与erastin和TRAIL处理过程中,BAX的寡聚化和其在线粒体的积累增加。有趣的是,联合处理促进的凋亡在BAX缺陷的HCT 116细胞中被有效抑制,但在BAK缺陷的细胞中没有。这些结果表明,BAX相关的BRA依赖性途径在erastin增强的TRAIL诱导的细胞凋亡中起着关键作用。
Ferroptosis is considered a distinctive form of cell death compared to other types of death such as apoptosis. It is known to result from iron-dependent accumulation of lipid peroxides rather than caspase activation. However, we reported recently that ferroptosis interplays with apoptosis. In this study, we investigated a possible mechanism of this interplay between ferroptosis and apoptosis. Results from our studies reveal that combined treatment of the ferroptotic agent erastin and the apoptotic agent TRAIL effectively disrupted mitochondrial membrane potential (ΔΨm) and subsequently promoted caspase activation. The alterations of mitochondrial membrane potential are probably due to an increase in oligomerization of BAX and its accumulation at the mitochondria during treatment with erastin and TRAIL. Interestingly, the combined treatment-promoted apoptosis was effectively inhibited in BAX-deficient HCT116 cells, but not BAK-deficient cells. These results indicate that the BAX-associated mitochondria-dependent pathway plays a pivotal role in erastin-enhanced TRAIL-induced apoptosis.
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