The mitochondrial intermembrane space protein mitofissin drives mitochondrial fission required for mitophagy
The mitochondrial intermembrane space protein mitofissin drives mitochondrial fission required for mitophagy
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DOI：
10.1016/j.molcel.2023.04.022
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发表时间：
2023-06-15
期刊：
影响因子：
16
通讯作者：
Kanki，Tomotake
中科院分区：
文献类型：
--
作者：
Fukuda，Tomoyuki;Furukawa，Kentaro;Kanki，Tomotake
线粒体自噬通过选择性降解线粒体在线粒体内环境稳定中起重要作用。在线粒体自噬过程中，线粒体应该被破碎以允许自噬体内的吞噬，自噬体的容量超过了典型的线粒体质量。然而，已知的线粒体分裂因子，酵母中的动力蛋白相关蛋白Dnm 1和哺乳动物中的DNM 1 L/Drp 1，与线粒体自噬无关。在这里，我们确定Atg 44作为一个线粒体分裂因子，是必不可少的线粒体自噬在酵母中，因此，我们术语Atg 44和它的orthopathic蛋白mitofissin。在有丝分裂素缺陷的细胞中，线粒体的一部分被线粒体自噬机制识别为货物，但由于缺乏线粒体分裂，不能被自噬体前体吞噬细胞吞噬。此外，我们表明，有丝分裂素直接结合到脂质膜，并带来脂质膜脆性，以促进膜分裂。综上所述，我们认为有丝分裂素直接作用于脂质膜，以驱动线粒体自噬所需的线粒体分裂。
Mitophagy plays an important role in mitochondrial homeostasis by selective degradation of mitochondria. During mitophagy, mitochondria should be fragmented to allow engulfment within autophagosomes, whose capacity is exceeded by the typical mitochondria mass. However, the known mitochondrial fission factors, dynamin-related proteins Dnm1 in yeasts and DNM1L/Drp1 in mammals, are dispensable for mitophagy. Here, we identify Atg44 as a mitochondrial fission factor that is essential for mitophagy in yeasts, and we therefore term Atg44 and its orthologous proteins mitofissin. In mitofissin-deficient cells, a part of the mitochondria is recognized by the mitophagy machinery as cargo but cannot be enwrapped by the autophagosome precursor, the phagophore, due to a lack of mitochondrial fission. Furthermore, we show that mitofissin directly binds to lipid membranes and brings about lipid membrane fragility to facilitate membrane fission. Taken together, we propose that mitofissin acts directly on lipid membranes to drive mitochondrial fission required for mitophagy.