Hurley James H, Young Lindsey N
Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, California, and Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720; email:
Annu Rev Biochem. 2017 Jun 20;86:225-244. doi: 10.1146/annurev-biochem-061516-044820. Epub 2017 Mar 15.
Autophagy is the process of cellular self-eating by a double-membrane organelle, the autophagosome. A range of signaling processes converge on two protein complexes to initiate autophagy: the ULK1 (unc51-like autophagy activating kinase 1) protein kinase complex and the PI3KC3-C1 (class III phosphatidylinositol 3-kinase complex I) lipid kinase complex. Some 90% of the mass of these large protein complexes consists of noncatalytic domains and subunits, and the ULK1 complex has essential noncatalytic activities. Structural studies of these complexes have shed increasing light on the regulation of their catalytic and noncatalytic activities in autophagy initiation. The autophagosome is thought to nucleate from vesicles containing the integral membrane protein Atg9 (autophagy-related 9), COPII (coat protein complex II) vesicles, and possibly other sources. In the wake of reconstitution and super-resolution imaging studies, we are beginning to understand how the ULK1 and PI3KC3-C1 complexes might coordinate the nucleation and fusion of Atg9 and COPII vesicles at the start of autophagosome biogenesis.
自噬是细胞通过一种双膜细胞器——自噬体进行自我吞噬的过程。一系列信号传导过程汇聚于两种蛋白质复合物以启动自噬：ULK1（类unc51自噬激活激酶1）蛋白激酶复合物和PI3KC3-C1（III类磷脂酰肌醇3-激酶复合物I）脂质激酶复合物。这些大型蛋白质复合物约90%的质量由非催化结构域和亚基组成，并且ULK1复合物具有重要的非催化活性。对这些复合物的结构研究越来越多地揭示了它们在自噬起始过程中催化和非催化活性的调控机制。自噬体被认为是从含有整合膜蛋白Atg9（自噬相关蛋白9）、COPII（II型被膜蛋白复合物）小泡以及可能的其他来源的小泡中形成的。在重组和超分辨率成像研究之后，我们开始了解ULK1和PI3KC3-C1复合物在自噬体生物发生起始阶段如何协调Atg9和COPII小泡的成核与融合。
