Role of Bax and Bak in mitochondrial morphogenesis
Role of Bax and Bak in mitochondrial morphogenesis
复制标题
DOI：
10.1038/nature05111
复制
发表时间：
2006-10-12
期刊：
影响因子：
64.8
通讯作者：
Youle, Richard J.
中科院分区：
文献类型：
--
作者：
Karbowski, Mariusz;Norris, Kristi L.;Youle, Richard J.
Bcl-2家族蛋白是程序性细胞死亡的有效调节剂。虽然它们在细胞内定位于线粒体和内质网，但它们如何发挥功能仍不清楚。Bcl-2家族的两个成员Bax和巴克在促进细胞凋亡的早期改变细胞内位置，以集中在线粒体分裂位点的焦点簇中。在这里，我们报告说，在健康的细胞Bax或巴克是所需的线粒体正常融合成细长的小管。Bax似乎诱导线粒体融合，通过激活组装的大GTP酶Mfn 2和改变其亚线粒体分布和膜流动性的特性，与不同的GTP结合状态的Mfn 2。我们的研究结果表明，Bax和巴克调节健康细胞中的线粒体动力学，并表明Bcl-2家族成员也可能通过细胞器形态发生机制调节细胞凋亡。
Bcl-2 family proteins are potent regulators of programmed cell death. Although their intracellular localization to mitochondria and the endoplasmic reticulum has focused research on these organelles, how they function remains unknown. Two members of the Bcl-2 family, Bax and Bak, change intracellular location early in the promotion of apoptosis to concentrate in focal clusters at sites of mitochondrial division. Here we report that in healthy cells Bax or Bak is required for normal fusion of mitochondria into elongated tubules. Bax seems to induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and changing its submitochondrial distribution and membrane mobility properties that correlate with different GTP-bound states of Mfn2. Our results show that Bax and Bak regulate mitochondrial dynamics in healthy cells and indicate that Bcl-2 family members may also regulate apoptosis through organelle morphogenesis machineries.