Ultrastructure and dynamics of the actin-myosin II cytoskeleton during mitochondrial fission
Ultrastructure and dynamics of the actin-myosin II cytoskeleton during mitochondrial fission
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DOI：
10.1038/s41556-019-0313-6
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发表时间：
2019-05-01
影响因子：
21.3
通讯作者：
Svitkina, Tatyana M.
中科院分区：
文献类型：
--
作者：
Yang, Changsong;Svitkina, Tatyana M.
线粒体裂变涉及细胞器的预收缩，随后由动力相关蛋白 Drp1 进行分裂。肌动蛋白和非肌肉肌球蛋白 II 通过一种尚不清楚的机制促进预收缩，这主要是由于线粒体收缩处未知的细胞骨架超微结构。在这里，使用铂复制品电子显微镜，我们发现细胞中的线粒体嵌入到含有丰富的无分支肌动蛋白丝的间质细胞骨架网络中。自发和诱导的线粒体收缩通常与构成该间质网络一部分的长肌动蛋白丝的纵横交错阵列相关。非肌肉肌球蛋白 II 被发现邻近线粒体，但在收缩位点并未特异性富集。在离子霉素诱导的线粒体裂变过程中，F-肌动蛋白云与线粒体收缩位点共定位，而动态肌球蛋白 II 云存在于收缩附近。我们提出，肌球蛋白 II 通过诱导间质肌动蛋白网络的随机变形来促进线粒体收缩，这对线粒体表面施加压力，从而启动完成线粒体收缩的曲率传感机制。
Mitochondrial fission involves the preconstriction of an organelle followed by scission by dynamin-related protein Drp1. Preconstriction is facilitated by actin and non-muscle myosin II through a mechanism that remains unclear, largely due to the unknown cytoskeletal ultrastructure at mitochondrial constrictions. Here, using platinum replica electron microscopy, we show that mitochondria in cells are embedded in an interstitial cytoskeletal network that contains abundant unbranched actin filaments. Both spontaneous and induced mitochondrial constrictions typically associate with a criss-cross array of long actin filaments that comprise part of this interstitial network. Non-muscle myosin II is found adjacent to mitochondria but is not specifically enriched at the constriction sites. During ionomycin-induced mitochondrial fission, F-actin clouds colocalize with mitochondrial constriction sites, whereas dynamic myosin II clouds are present in the vicinity of constrictions. We propose that myosin II promotes mitochondrial constriction by inducing stochastic deformations of the interstitial actin network, which applies pressure on the mitochondrial surface and thus initiates curvature-sensing mechanisms that complete mitochondrial constriction.