凋亡过程中 Bax 与线粒体分裂位点、动力相关蛋白 1（Drp1）和线粒体融合蛋白 2（Mfn2）的时空关联。
Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis.
作者信息
Karbowski Mariusz, Lee Yang-Ja, Gaume Brigitte, Jeong Seon-Yong, Frank Stephan, Nechushtan Amotz, Santel Ansgar, Fuller Margaret, Smith Carolyn L, Youle Richard J
机构信息
Biochemistry Section, SNB, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
J Cell Biol. 2002 Dec 23;159(6):931-8. doi: 10.1083/jcb.200209124.
We find that Bax, a proapoptotic member of the Bcl-2 family, translocates to discrete foci on mitochondria during the initial stages of apoptosis, which subsequently become mitochondrial scission sites. A dominant negative mutant of Drp1, Drp1K38A, inhibits apoptotic scission of mitochondria, but does not inhibit Bax translocation or coalescence into foci. However, Drp1K38A causes the accumulation of mitochondrial fission intermediates that are associated with clusters of Bax. Surprisingly, Drp1 and Mfn2, but not other proteins implicated in the regulation of mitochondrial morphology, colocalize with Bax in these foci. We suggest that Bax participates in apoptotic fragmentation of mitochondria.
我们发现，Bcl-2家族的促凋亡成员Bax在凋亡初始阶段会转位至线粒体上离散的聚集点，这些聚集点随后成为线粒体分裂位点。动力相关蛋白1（Drp1）的显性负性突变体Drp1K38A可抑制线粒体的凋亡分裂，但不抑制Bax的转位或聚集成簇。然而，Drp1K38A会导致与Bax簇相关的线粒体分裂中间体的积累。令人惊讶的是，Drp1和线粒体融合蛋白2（Mfn2），而非其他参与线粒体形态调控的蛋白质，在这些聚集点与Bax共定位。我们认为，Bax参与了线粒体的凋亡性断裂。
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