Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.
Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.
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DOI：
10.1016/j.devcel.2018.01.007
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发表时间：
2018-02-26
影响因子：
11.8
通讯作者：
Buss F
中科院分区：
文献类型：
--
作者：
Kruppa AJ;Kishi-Itakura C;Masters TA;Rorbach JE;Grice GL;Kendrick-Jones J;Nathan JA;Minczuk M;Buss F
线粒体质量控制对于维持细胞内稳态是必不可少的，并且通过经由帕金森介导的线粒体自噬去除受损的、泛素化的线粒体来实现。在这里，我们证明了MYO 6（肌球蛋白VI），一种独特的肌球蛋白，移动到肌动蛋白丝的负端，与帕金形成复合物，并通过其泛素结合结构域选择性地招募到受损的线粒体。这种肌球蛋白马达启动F-肌动蛋白笼的组装，通过形成物理屏障来包裹受损的线粒体，从而防止与邻近群体的再融合。MYO 6的缺失导致线粒体吞噬体的积累和线粒体质量的增加。此外，我们观察到下游线粒体功能障碍表现为呼吸能力降低和依赖氧化磷酸化产生能量的能力降低。我们的工作揭示了线粒体质量控制的关键步骤：MYO 6依赖性肌动蛋白笼的形成，确保受损线粒体从网络中分离出来。MYO 6与帕金形成复合物并被募集到受损的线粒体MYO 6触发功能障碍的线粒体周围的F-肌动蛋白笼组装肌动蛋白笼形成屏障，从而防止受损线粒体的再融合MYO 6的缺失导致线粒体吞噬体的积累和线粒体功能障碍Kruppa et al.证明MYO 6与帕金形成复合物，并被招募到受损的泛素化线粒体。MYO 6促进F-肌动蛋白笼组装，以隔离和防止功能失调的细胞器的再融合。MYO 6的缺失导致线粒体自噬缺陷，伴随线粒体自噬体的积累和下游线粒体功能障碍。
Mitochondrial quality control is essential to maintain cellular homeostasis and is achieved by removing damaged, ubiquitinated mitochondria via Parkin-mediated mitophagy. Here, we demonstrate that MYO6 (myosin VI), a unique myosin that moves toward the minus end of actin filaments, forms a complex with Parkin and is selectively recruited to damaged mitochondria via its ubiquitin-binding domain. This myosin motor initiates the assembly of F-actin cages to encapsulate damaged mitochondria by forming a physical barrier that prevents refusion with neighboring populations. Loss of MYO6 results in an accumulation of mitophagosomes and an increase in mitochondrial mass. In addition, we observe downstream mitochondrial dysfunction manifesting as reduced respiratory capacity and decreased ability to rely on oxidative phosphorylation for energy production. Our work uncovers a crucial step in mitochondrial quality control: the formation of MYO6-dependent actin cages that ensure isolation of damaged mitochondria from the network. MYO6 forms a complex with Parkin and is recruited to damaged mitochondria MYO6 triggers F-actin cage assembly around dysfunctional mitochondria Actin cages form a barrier thereby preventing refusion of damaged mitochondria Loss of MYO6 causes an accumulation of mitophagosomes and mitochondrial dysfunction Kruppa et al. demonstrate that MYO6 forms a complex with Parkin and is recruited to damaged, ubiquitinated mitochondria. MYO6 promotes F-actin cage assembly to isolate and prevent refusion of dysfunctional organelles. Loss of MYO6 leads to a mitophagy defect with an accumulation of mitophagosomes and downstream mitochondrial dysfunction.
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影响因子：
9.2
作者：
Korobova, Farida;Gauvin, Timothy J.;Higgs, Henry N.
通讯作者：
Higgs, Henry N.
在生长因子刺激后，肌球蛋白VI在高尔基体复合物和成纤维细胞的前缘及其磷酸化和募集到A431细胞的膜褶皱中的定位。
影响因子：
7.8
作者：
Buss, F;Kendrick-Jones, J;Lionne, C;Knight, A E;Cote, G P;Paul Luzio, J
通讯作者：
Paul Luzio, J
影响因子：
4
作者：
Chibalina, Margarita V.;Seaman, Matthew N. J.;Miller, Christopher C.;Kendrick-Jones, John;Buss, Folma
通讯作者：
Buss, Folma
影响因子：
16
作者：
Heo JM;Ordureau A;Paulo JA;Rinehart J;Harper JW
通讯作者：
Harper JW
影响因子：
21.3
作者：
Fallon, Lara;Belanger, Catherine M. L.;Fon, Edward A.
通讯作者：
Fon, Edward A.