Drosophila MIC60/mitofilin conducts dual roles in mitochondrial motility and crista structure.
Drosophila MIC60/mitofilin conducts dual roles in mitochondrial motility and crista structure.
复制标题
DOI：
10.1091/mbc.e17-03-0177
复制
发表时间：
2017-11-15
影响因子：
3.3
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Tsai PI;Papakyrikos AM;Hsieh CH;Wang X
线粒体是为细胞提供能量的重要细胞器。已知MIC 60/丝裂素对于维持解离细胞中的线粒体结构是重要的;然而，其在完整动物中的生理作用尚不清楚。在这项研究中，我们解开删除MIC 60/丝裂素在果蝇的功能后果。MIC 60/mitofilin在线粒体内膜上构成异源寡聚复合物以维持嵴结构。然而，人们对其生理功能知之甚少。在这里，通过描述果蝇MIC 60突变体，我们定义其在体内的作用。我们发现MIC 60具有维持线粒体稳态的双重功能。除了其在嵴膜结构中的典型作用外，MIC 60可能通过影响将线粒体锚定到微管马达的线粒体外膜蛋白Miro的蛋白质水平来调节线粒体运动。MIC 60的丧失导致Miro丧失和线粒体停滞。在细胞水平上，MIC 60的缺失会破坏神经肌肉接头的突触结构和功能。MIC 60在线粒体嵴结构和运动性中的双重作用使其成为细胞完整性和存活的关键参与者。
Mitochondria are crucial organelles for providing energy for a cell. It is known that MIC60/mitofilin is important for maintaining mitochondrial structure in dissociated cells; however, its physiological roles in an intact animal are less clear. In this study, we unravel the functional consequences of deleting MIC60/mitofilin in fruit flies. MIC60/mitofilin constitutes a hetero-oligomeric complex on the inner mitochondrial membranes to maintain crista structure. However, little is known about its physiological functions. Here, by characterizing Drosophila MIC60 mutants, we define its roles in vivo. We discover that MIC60 performs dual functions to maintain mitochondrial homeostasis. In addition to its canonical role in crista membrane structure, MIC60 regulates mitochondrial motility, likely by influencing protein levels of the outer mitochondrial membrane protein Miro that anchors mitochondria to the microtubule motors. Loss of MIC60 causes loss of Miro and mitochondrial arrest. At a cellular level, loss of MIC60 disrupts synaptic structure and function at the neuromuscular junctions. The dual roles of MIC60 in both mitochondrial crista structure and motility position it as a crucial player for cellular integrity and survival.