A role for myosin II in mammalian mitochondrial fission.
A role for myosin II in mammalian mitochondrial fission.
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DOI：
10.1016/j.cub.2013.12.032
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发表时间：
2014-02-17
期刊：
影响因子：
9.2
通讯作者：
Higgs, Henry N.
中科院分区：
文献类型：
--
作者：
Korobova, Farida;Gauvin, Timothy J.;Higgs, Henry N.
线粒体是一种动态的细胞器，在分裂间期细胞中有规律地发生分裂和融合。线粒体分裂被认为是质量控制机制的一部分，其中受损的线粒体组分与个体线粒体中的健康组分分离，随后是线粒体分裂和受损子体线粒体的降解。裂变也在细胞凋亡中起作用。线粒体动力学的缺陷可能导致神经退行性疾病，如阿尔茨海默氏症。线粒体分裂需要动力蛋白GTdR Drp 1，它在线粒体周围聚集成一个环，似乎可以收缩线粒体的内外膜。然而，哺乳动物线粒体上Drp1组装的控制机制尚不清楚。最近的研究结果表明，肌动蛋白聚合，驱动内质网结合蛋白INF 2，刺激Drp1在裂变位点组装。在这里，我们表明，肌球蛋白II也在裂变中发挥作用。通过blebbistatin或siRNA介导的抑制肌球蛋白IIA或肌球蛋白IIB的化学抑制导致对照细胞和表达组成型活性INF 2的细胞中线粒体长度增加。活性肌球蛋白II以肌动蛋白和INF 2依赖的方式在线粒体上的斑点中积累。此外，肌球蛋白II抑制减少Drp1与线粒体的关联。基于这些结果，我们提出了一个机制模型，其中INF 2介导的肌动蛋白聚合导致肌球蛋白II的招聘和收缩在裂变位点，增强随后Drp1的积累和裂变。
Mitochondria are dynamic organelles, undergoing both fission and fusion regularly in interphase cells. Mitochondrial fission is thought to be part of a quality control mechanism, whereby damaged mitochondrial components are segregated from healthy components in an individual mitochondrion, followed by mitochondrial fission and degradation of the damaged daughter mitochondrion. Fission also plays a role in apoptosis. Defects in mitochondrial dynamics can lead to neurodegenerative diseases such as Alzheimer’s. Mitochondrial fission requires the dynamin GTPase Drp1, which assembles in a ring around the mitochondrion and appears to constrict both outer and inner mitochondrial membranes. However, mechanisms controlling Drp1 assembly on mammalian mitochondria are unclear. Recent results show that actin polymerization, driven by the endoplasmic reticulum-bound formin protein INF2, stimulates Drp1 assembly at fission sites. Here, we show that myosin II also plays a role in fission. Chemical inhibition by blebbistatin or siRNA-mediated suppression of myosin IIA or myosin IIB causes an increase in mitochondrial length in both control cells and cells expressing constitutively active INF2. Active myosin II accumulates in puncta on mitochondria in an actin- and INF2-dependent manner. In addition, myosin II inhibition decreases Drp1 association with mitochondria. Based on these results, we propose a mechanistic model in which INF2-mediated actin polymerization leads to myosin II recruitment and constriction at the fission site, enhancing subsequent Drp1 accumulation and fission.
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DOI：
10.1523/jneurosci.1621-10.2010
发表时间：
2010-06-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Pathak D;Sepp KJ;Hollenbeck PJ
通讯作者：
Hollenbeck PJ
影响因子：
4.8
作者：
Palmer, Catherine S.;Elgass, Kirstin D.;Ryan, Michael T.
通讯作者：
Ryan, Michael T.
影响因子：
11.4
作者：
Collins, TJ;Berridge, MJ;Bootman, MD
通讯作者：
Bootman, MD
影响因子：
5.2
作者：
Chang CR;Blackstone C
通讯作者：
Blackstone C
影响因子：
16.2
作者：
DuBoff B;Götz J;Feany MB
通讯作者：
Feany MB