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Abstract：
Recent studies show that mitochondria and actin filaments work together in two contexts: (1) increased cytoplasmic calcium induces cytoplasmic actin polymerization that stimulates mitochondrial fission and (2) mitochondrial depolarization causes actin assembly around mitochondria, with roles in mitophagy. It is unclear whether these two processes utilize similar actin assembly mechanisms. Here, we show that these are distinct actin assembly mechanisms in the acute phase after treatment (<10 min). Calcium-induced actin assembly is INF2 dependent and Arp2/3 complex independent, whereas depolarization-induced actin assembly is Arp2/3 complex dependent and INF2 independent. The two types of actin polymerization are morphologically distinct, with calcium-induced filaments throughout the cytosol and depolarization-induced filaments as \'clouds\' around depolarized mitochondria. We have previously shown that calcium-induced actin stimulates increases in both mitochondrial calcium and recruitment of the dynamin GTPase Drp1 (also known as DNM1L). In contrast, depolarization-induced actin is temporally associated with extensive mitochondrial dynamics that do not result in mitochondrial fission, but in circularization of the inner mitochondrial membrane (IMM). These dynamics are dependent on the protease OMA1 and independent of Drp1. Actin cloud inhibition causes increased IMM circularization, suggesting that actin clouds limit these dynamics.This article has an associated First Person interview with the first author of the paper.
摘要：
最近的研究表明，线粒体和肌动蛋白丝在两种情况下一起工作：（1）增加的细胞质钙诱导刺激线粒体裂变的细胞质肌动蛋白聚合和（2）线粒体去极化导致线粒体周围的肌动蛋白组装，在线粒体自噬中起作用。尚不清楚这两个过程是否利用相似的肌动蛋白组装机制。这里,我们发现这些是治疗后急性期（<10分钟）不同的肌动蛋白组装机制。钙诱导的肌动蛋白组装是INF2依赖性和Arp2/3复合物独立的，而去极化诱导的肌动蛋白组装是Arp2/3复合物依赖性和INF2依赖性。两种类型的肌动蛋白聚合在形态上是不同的，在整个胞质溶胶中具有钙诱导的细丝，在去极化的线粒体周围具有去极化诱导的细丝。我们先前已经表明，钙诱导的肌动蛋白刺激线粒体钙的增加和动态蛋白GTP酶Drp1（也称为DNM1L）的募集。相比之下,去极化诱导的肌动蛋白在时间上与广泛的线粒体动力学相关，不会导致线粒体裂变，而是在线粒体内膜（IMM）的环化中。这些动力学依赖于蛋白酶OMA1并且不依赖于Drp1。肌动蛋白云抑制导致IMM环化增加，表明肌动蛋白云限制了这些动力学。本文与该论文的第一作者进行了相关的第一人称访谈。
