The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy
The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy
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DOI：
10.1091/mbc.e07-12-1257
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发表时间：
2008-05-01
影响因子：
3.3
通讯作者：
Yoshimori, Tamotsu
中科院分区：
文献类型：
--
作者：
Fujita, Naonobu;Itoh, Takashi;Yoshimori, Tamotsu
两种泛素样分子 Atg12 和 LC3/Atg8 参与自噬体生物发生。 Atg12 与 Atg5 缀合，与 Atg16L 形成类似 800 kDa 的蛋白质复合物（简称 Atg16L 复合物）。 LC3/Atg8 与磷脂酰乙醇胺缀合，并与自噬体形成相关，可能是通过使膜伸长来实现的。尽管 Atg16L 复合物是有效 LC3 脂化所必需的，但其作用尚不清楚。在这里，我们发现 Atg12 或 Atg16L 的过度表达会抑制自噬体的形成。从机制上讲，LC3 脂化的位点由 Atg16L 复合物的膜定位以及 Atg12 与 Atg3（LC3 脂化过程中的 E2 酶）的相互作用决定。 Atg16L 强制定位于质膜，使得该位点能够发生异位 LC3 脂化。我们认为 Atg16L 复合物是一种新型 E3 样酶，通过动态定位到自噬体形成的推定来源膜，充当 LC3 脂化的支架。
Two ubiquitin-like molecules, Atg12 and LC3/Atg8, are involved in autophagosome biogenesis. Atg12 is conjugated to Atg5 and forms an similar to 800-kDa protein complex with Atg16L ( referred to as Atg16L complex). LC3/Atg8 is conjugated to phosphatidylethanolamine and is associated with autophagosome formation, perhaps by enabling membrane elongation. Although the Atg16L complex is required for efficient LC3 lipidation, its role is unknown. Here, we show that overexpression of Atg12 or Atg16L inhibits autophagosome formation. Mechanistically, the site of LC3 lipidation is determined by the membrane localization of the Atg16L complex as well as the interaction of Atg12 with Atg3, the E2 enzyme for the LC3 lipidation process. Forced localization of Atg16L to the plasma membrane enabled ectopic LC3 lipidation at that site. We propose that the Atg16L complex is a new type of E3-like enzyme that functions as a scaffold for LC3 lipidation by dynamically localizing to the putative source membranes for autophagosome formation.