由 ER 相关形态发生因子 INF2 介导的线粒体裂变中的肌动蛋白依赖步骤。
An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2.
机构信息
Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
出版信息
Science. 2013 Jan 25;339(6118):464-7. doi: 10.1126/science.1228360.
Abstract
Mitochondrial fission is fundamentally important to cellular physiology. The dynamin-related protein Drp1 mediates fission, and interaction between mitochondrion and endoplasmic reticulum (ER) enhances fission. However, the mechanism for Drp1 recruitment to mitochondria is unclear, although previous results implicate actin involvement. Here, we found that actin polymerization through ER-localized inverted formin 2 (INF2) was required for efficient mitochondrial fission in mammalian cells. INF2 functioned upstream of Drp1. Actin filaments appeared to accumulate between mitochondria and INF2-enriched ER membranes at constriction sites. Thus, INF2-induced actin filaments may drive initial mitochondrial constriction, which allows Drp1-driven secondary constriction. Because INF2 mutations can lead to Charcot-Marie-Tooth disease, our results provide a potential cellular mechanism for this disease state.
摘要
线粒体分裂对细胞生理学至关重要。与线粒体和内质网（ER）相互作用的动力相关蛋白 1（Drp1）介导分裂。然而，Drp1 招募到线粒体的机制尚不清楚，尽管先前的结果表明肌动蛋白参与其中。在这里，我们发现哺乳动物细胞中线粒体分裂需要通过内质网定位的反向formin 2（INF2）进行肌动蛋白聚合。INF2 在 Drp1 之前起作用。在收缩部位，肌动蛋白丝似乎在 INF2 富集的 ER 膜和线粒体之间积累。因此，INF2 诱导的肌动蛋白丝可能驱动初始线粒体收缩，从而允许 Drp1 驱动二次收缩。由于 INF2 突变可导致 Charcot-Marie-Tooth 病，我们的结果为该疾病状态提供了一种潜在的细胞机制。
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