Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission
Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission
复制标题
DOI：
10.1016/j.cub.2005.02.064
复制
发表时间：
2005-04-12
期刊：
影响因子：
9.2
通讯作者：
Sheetz, MP
中科院分区：
文献类型：
--
作者：
De Vos, KJ;Allan, VJ;Sheetz, MP
线粒体呈现多种形状，从小而球形或经典的管状到延伸的网络不等[1,2]。形状转变频繁发生，包括融合、分裂和分支[3]。据报道，一些线粒体形状转变受发育调控[4,5]，而其他的则与疾病[6 - 9]或细胞凋亡[10,11]有关。然而，线粒体功能是否以及如何通过调节线粒体分裂和融合来控制线粒体形状尚不清楚。在此，我们表明电子传递抑制剂、ATP合酶抑制剂或通透性转换孔（mtPTP）可诱导可逆的线粒体分裂。线粒体分裂依赖于动力相关蛋白1（DRP1）和F - 肌动蛋白：F - 肌动蛋白的破坏减弱了分裂以及DRP1向线粒体的募集。相反，电子传递和氧化磷酸化的解偶联导致线粒体呈现一种独特的圆盘状。这种形状变化不依赖于细胞骨架和DRP1，很可能是由肿胀引起的。因此，线粒体功能的破坏通过激活依赖于DRP1的分裂或通过肿胀迅速且可逆地改变线粒体形状，这表明线粒体分裂、形状和功能之间存在密切关系。此外，我们的结果表明肌动蛋白细胞骨架通过促进DRP1向线粒体的募集而参与线粒体分裂。
Mitochondria display a variety of shapes, ranging from small and spherical or the classical tubular shape to extended networks [1, 2]. Shape transitions occur frequently and include fusion, fission, and branching [3]. It was reported that some mitochondrial shape transitions are developmentally regulated [4, 5], whereas others were linked to disease [6-9] or apoptosis [10, 11]. However, if and how mitochondrial function controls mitochondrial shape through regulation of mitochondrial fission and fusion is unclear. Here, we show that inhibitors of electron transport, ATP synthase, or the permeability transition pore (mtPTP) induced reversible mitochondrial fission. Mitochondrial fission depended on dynamin-related protein 1 (DRP1) and F-actin: Disruption of F-actin attenuated fission and recruitment of DRP1 to mitochondria. In contrast, uncoupling of electron transport and oxidative phosphorylation caused mitochondria to adopt a distinct disk shape. This shape change was independent of the cytoskeleton and DRP1 and was most likely caused by swelling. Thus, disruption of mitochondrial function rapidly and reversibly altered mitochondrial shape either by activation of DRP1-dependent fission or by swelling, indicating a close relationship between mitochondrial fission, shape, and function. Furthermore, our results suggest that the actin cytoskeleton is involved in mitochondrial fission by facilitating mitochondrial recruitment of DRP1.