Wang Lan, Walter Peter
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94143, USA; email:
Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94122, USA.
Annu Rev Cell Dev Biol. 2020 Oct 6;36:141-164. doi: 10.1146/annurev-cellbio-031220-015840. Epub 2020 Sep 4.
Mitochondrial function depends on the efficient import of proteins synthesized in the cytosol. When cells experience stress, the efficiency and faithfulness of the mitochondrial protein import machinery are compromised, leading to homeostatic imbalances and damage to the organelle. Yeast Msp1 (mitochondrial sorting of proteins 1) and mammalian ATAD1 (ATPase family AAA domain-containing 1) are orthologous AAA proteins that, fueled by ATP hydrolysis, recognize and extract mislocalized membrane proteins from the outer mitochondrial membrane. Msp1 also extracts proteins that have become stuck in the import channel. The extracted proteins are targeted for proteasome-dependent degradation or, in the case of mistargeted tail-anchored proteins, are given another chance to be routed correctly. In addition, ATAD1 is implicated in the regulation of synaptic plasticity, mediating the release of neurotransmitter receptors from postsynaptic scaffolds to allow their trafficking. Here we discuss how structural and functional specialization imparts the unique properties that allow Msp1/ATAD1 ATPases to fulfill these diverse functions and also highlight outstanding questions in the field.
线粒体功能依赖于胞质溶胶中合成的蛋白质的有效导入。当细胞受到应激时，线粒体蛋白质导入机制的效率和忠实性会受到损害，导致体内平衡失衡和细胞器损伤。酵母Msp1（蛋白质线粒体分选1）和哺乳动物ATAD1（含ATP酶家族AAA结构域1）是直系同源的AAA蛋白，它们在ATP水解的驱动下，识别并从线粒体外膜中提取错误定位的膜蛋白。Msp1还能提取卡在导入通道中的蛋白质。提取的蛋白质会被靶向蛋白酶体依赖性降解，或者对于错误定位的尾锚定蛋白，会有机会再次被正确转运。此外，ATAD1参与突触可塑性的调节，介导神经递质受体从突触后支架的释放，以使其能够进行运输。在这里，我们讨论结构和功能特化如何赋予Msp1/ATAD1 ATP酶独特的特性，使其能够履行这些不同的功能，并突出该领域尚未解决的问题。
