Adaptor Proteins MiD49 and MiD51 Can Act Independently of Mff and Fis1 in Drp1 Recruitment and Are Specific for Mitochondrial Fission
Adaptor Proteins MiD49 and MiD51 Can Act Independently of Mff and Fis1 in Drp1 Recruitment and Are Specific for Mitochondrial Fission
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DOI：
10.1074/jbc.m113.479873
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发表时间：
2013-09-20
影响因子：
4.8
通讯作者：
Ryan, Michael T.
中科院分区：
文献类型：
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作者：
Palmer, Catherine S.;Elgass, Kirstin D.;Ryan, Michael T.
drp 1（动力蛋白相关蛋白1）被募集到线粒体和过氧化物酶体膜上以执行裂变。Fis 1和Mff是线粒体和过氧化物酶体的Drp 1受体/效应蛋白。最近，MiD 49和MiD 51也被证明可以将Drp 1募集到线粒体表面;然而，不同的报道认为它们在裂变和融合中起着相反的作用。在这里，我们表明，MiD 49或MiD 51过表达阻断裂变的作用，在显性负的方式，通过螯合Drp 1特异性在线粒体，导致unopposed融合事件在线粒体沿着延长过氧化物酶体。MiD 49/51过表达引起的线粒体延长需要融合介质线粒体融合蛋白1和2的作用。此外，当MiD 49和MiD 51在线粒体上形成离散灶时，在低水平过表达下，仍然发生线粒体分裂事件。与Fis 1和Mff不同，MiD 49和MiD 51不靶向过氧化物酶体表面，这表明它们特异性地促进线粒体上Drp 1定向的裂变。此外，当MiD 49或MiD 51靶向过氧化物酶体或溶酶体的表面时，Drp 1被特异性地募集到这些细胞器。此外，MiD 49/51的Drp 1募集活性似乎强于Mff或Fis 1。我们的结论是，MiD 49和MiD 51可以独立的Mff和Fis 1在Drp 1招聘，并建议他们提供特异性的线粒体分裂。
Drp1 (dynamin-related protein 1) is recruited to both mitochondrial and peroxisomal membranes to execute fission. Fis1 and Mff are Drp1 receptor/effector proteins of mitochondria and peroxisomes. Recently, MiD49 and MiD51 were also shown to recruit Drp1 to the mitochondrial surface; however, different reports have ascribed opposing roles in fission and fusion. Here, we show that MiD49 or MiD51 overexpression blocked fission by acting in a dominant-negative manner by sequestering Drp1 specifically at mitochondria, causing unopposed fusion events at mitochondria along with elongation of peroxisomes. Mitochondrial elongation caused by MiD49/51 overexpression required the action of fusion mediators mitofusins 1 and 2. Furthermore, at low level overexpression when MiD49 and MiD51 form discrete foci at mitochondria, mitochondrial fission events still occurred. Unlike Fis1 and Mff, MiD49 and MiD51 were not targeted to the peroxisomal surface, suggesting that they specifically act to facilitate Drp1-directed fission at mitochondria. Moreover, when MiD49 or MiD51 was targeted to the surface of peroxisomes or lysosomes, Drp1 was specifically recruited to these organelles. Moreover, the Drp1 recruitment activity of MiD49/51 appeared stronger than that of Mff or Fis1. We conclude that MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and suggest that they provide specificity to the division of mitochondria.