The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells
The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells
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DOI：
10.1091/mbc.e07-12-1287
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发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
van der Bliek, Alexander M.
中科院分区：
文献类型：
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作者：
Gandre-Babbe, Shilpa;van der Bliek, Alexander M.
线粒体分裂机制的组成部分很少是已知的，尽管线粒体分裂是一个对细胞生长和存活至关重要的复杂过程。在这里，我们描述了一种新的蛋白质，控制线粒体分裂。该蛋白质是在使用果蝇细胞的小干扰RNA（siRNA）筛选中鉴定的。这种蛋白质的人类同源物被命名为线粒体分裂因子（Mff）。用Mff siRNA转染的细胞的线粒体形成闭合网络，其类似于当细胞用针对两种已建立的裂变蛋白Drp1和Fis1的siRNA转染时形成的线粒体网络。与Drp1和Fis1 siRNA一样，Mff siRNA也抑制由线粒体膜电位丧失诱导的分裂，它延迟细胞色素c从线粒体释放和细胞凋亡的进一步进展，并且它抑制过氧化物酶体分裂。Mff和Fis1都是尾锚定在线粒体外膜上，但这些蛋白质的其他部分非常不同，它们存在于单独的200 kDa复合物中，这表明它们在裂变过程中发挥不同的作用。我们的结论是，MFF是一个保守的膜裂变途径的组成和诱导线粒体和过氧化物酶体的裂变的一个新的组成部分。
Few components of the mitochondrial fission machinery are known, even though mitochondrial fission is a complex process of vital importance for cell growth and survival. Here, we describe a novel protein that controls mitochondrial fission. This protein was identified in a small interfering RNA (siRNA) screen using Drosophila cells. The human homologue of this protein was named Mitochondrial fission factor (Mff). Mitochondria of cells transfected with Mff siRNA form a closed network similar to the mitochondrial networks formed when cells are transfected with siRNA for two established fission proteins, Drp1 and Fis1. Like Drp1 and Fis1 siRNA, Mff siRNA also inhibits fission induced by loss of mitochondrial membrane potential, it delays cytochrome c release from mitochondria and further progression of apoptosis, and it inhibits peroxisomal fission. Mff and Fis1 are both tail anchored in the mitochondrial outer membrane, but other parts of these proteins are very different and they exist in separate 200-kDa complexes, suggesting that they play different roles in the fission process. We conclude that Mff is a novel component of a conserved membrane fission pathway used for constitutive and induced fission of mitochondria and peroxisomes.