Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles.
Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles.
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DOI：
10.1038/ncomms12420
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发表时间：
2016-08-11
影响因子：
16.6
通讯作者：
Ktistakis NT
中科院分区：
文献类型：
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作者：
Karanasios E;Walker SA;Okkenhaug H;Manifava M;Hummel E;Zimmermann H;Ahmed Q;Domart MC;Collinson L;Ktistakis NT
自噬体的形成需要自噬特异性蛋白质连续移位到富含PI3P并连接到ER的膜。在此之前，从头形成的最早的自噬特异性结构是ULK1复合物的小斑点。这个结构的起源和形成方式尚不清楚。我们表明，ULK1结构出现的区域，其中ATG9囊泡与ER对齐，其形成需要ER退出和coatomer功能。超分辨率显微镜显示，ULK1区室由规则组装的点状元件组成，这些元件聚集在逐渐变大的球形结构中，并与早期自噬机制独特地相关。相关的电子显微镜后，现场成像显示tubulovesicular膜存在于这个结构的位置。我们提出自噬体的成核发生在ULK1复合物与ER和ATG 9隔室结合的区域。 ULK1复合物在自噬体成核过程中是必需的，但自噬膜的起始位置尚不清楚。在这里，作者使用超分辨率显微镜提出自噬体起源于ER中的管状囊泡结构，与ATG 9囊泡对齐并招募ULK 1。
Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment. The ULK1 complex is required during autophagosome nucleation, but where autophagic membranes initiate is unknown. Here the authors use super-resolution microscopy to propose that autophagosomes originate from tubulovesicular structures in the ER that align with ATG9 vesicles and recruit ULK1.