Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis.
Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis.
复制标题
Bax和Bak可以定位于内质网状以启动凋亡。
DOI：
10.1083/jcb.200302084
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发表时间：
2003-07-07
影响因子：
7.8
通讯作者：
Thompson, Craig B
中科院分区：
文献类型：
--
作者：
Zong, Wei-Xing;Li, Chi;Hatzivassiliou, Georgia;Lindsten, Tullia;Yu, Qian-Chun;Yuan, Junying;Thompson, Craig B
Bax 和 Bak 在线粒体释放凋亡因子引发的细胞凋亡中发挥着多余但重要的作用。 Bax 和 Bak 除了存在于线粒体外膜外，还可以定位于 ER。启动内质网应激反应的药物可以诱导内质网和线粒体上 Bax 的构象变化和寡聚化。在野生型细胞中，这与 caspase 12 裂解有关，而 caspase 12 裂解在 bax - / - bak - / - 细胞中被消除。在bax - / - bak - / - 细胞中，引入选择性靶向线粒体或ER的Bak突变体可以诱导细胞凋亡。然而，Bak 是针对 ER 的，而不是针对线粒体的，它会导致 ER Ca2+ 逐渐耗尽，并诱导 caspase 12 裂解。相反，与靶向 ER 的 Bak 相比，靶向线粒体的 Bak 导致 caspase 7 和 PARP 裂解增强。这些发现表明，除了在线粒体中发挥作用外，Bax 和 Bak 还定位于 ER，并具有启动 caspase 激活和细胞凋亡的并行途径的功能。
Bax and Bak play a redundant but essential role in apoptosis initiated by the mitochondrial release of apoptogenic factors. In addition to their presence at the mitochondrial outer membrane, Bax and Bak can also localize to the ER. Agents that initiate ER stress responses can induce conformational changes and oligomerization of Bax on the ER as well as on mitochondria. In wild-type cells, this is associated with caspase 12 cleavage that is abolished in bax − / − bak − / − cells. In bax − / − bak − / − cells, introduction of Bak mutants selectively targeted to either mitochondria or the ER can induce apoptosis. However, ER-targeted, but not mitochondria-targeted, Bak leads to progressive depletion of ER Ca2+ and induces caspase 12 cleavage. In contrast, mitochondria-targeted Bak leads to enhanced caspase 7 and PARP cleavage in comparison with the ER-targeted Bak. These findings demonstrate that in addition to their functions at mitochondria, Bax and Bak also localize to the ER and function to initiate a parallel pathway of caspase activation and apoptosis.