Dynamics of nucleoid structure regulated by mitochondrial fission contributes to cristae reformation and release of cytochrome c
Dynamics of nucleoid structure regulated by mitochondrial fission contributes to cristae reformation and release of cytochrome c
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DOI：
10.1073/pnas.1301951110
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发表时间：
2013-07-16
影响因子：
11.1
通讯作者：
Ishihara, Naotada
中科院分区：
文献类型：
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作者：
Ban-Ishihara, Reiko;Ishihara, Takaya;Ishihara, Naotada
哺乳动物细胞通常含有数千个线粒体DNA拷贝，组装成数百个类核。在这里，我们分析了动态特征的类核的线粒体膜动力学涉及平衡融合和分裂。在线粒体分裂GTdR动力蛋白相关蛋白（Drp 1）缺陷细胞，类核扩大了他们的集群内超灌注线粒体。在正常细胞中，线粒体分裂经常发生在类核附近，因为Mff和Drp 1的定位依赖于类核。因此，线粒体分裂相邻的类核，应防止他们的集群保持小而破碎的类核。增强的类核聚集导致在扩大的球状线粒体（线粒体球）中形成高度堆叠的嵴结构。外壳的促凋亡因子细胞色素c，但不是Smac/DIABLO，到高度堆叠的嵴抑制其释放的线粒体凋亡刺激下。在没有类核的情况下，Drp 1缺陷不能形成线粒体球和防止细胞凋亡。因此，通过分裂和融合的线粒体动力学在控制线粒体类核结构中起关键作用，有助于线粒体的嵴重建和促凋亡状态。
Mammalian cells typically contain thousands of copies of mitochondrial DNA assembled into hundreds of nucleoids. Here we analyzed the dynamic features of nucleoids in terms of mitochondrial membrane dynamics involving balanced fusion and fission. In mitochondrial fission GTPase dynamin-related protein (Drp1)-deficient cells, nucleoids were enlarged by their clustering within hyperfused mitochondria. In normal cells, mitochondrial fission often occurred adjacent to nucleoids, since localization of Mff and Drp1 is dependent on the nucleoids. Thus, mitochondrial fission adjacent to nucleoids should prevent their clustering by maintaining small and fragmented nucleoids. The enhanced clustering of nucleoids resulted in the formation of highly stacked cristae structures in enlarged bulb-like mitochondria (mito-bulbs). Enclosure of proapoptotic factor cytochrome c, but not of Smac/DIABLO, into the highly stacked cristae suppressed its release from mitochondria under apoptotic stimuli. In the absence of nucleoids, Drp1 deficiency failed to form mito-bulbs and to protect against apoptosis. Thus, mitochondrial dynamics by fission and fusion play a critical role in controlling mitochondrial nucleoid structures, contributing to cristae reformation and the proapoptotic status of mitochondria.