Vac8 spatially confines autophagosome formation at the vacuole in S. cerevisiae
Vac8 spatially confines autophagosome formation at the vacuole in S. cerevisiae
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DOI：
10.1242/jcs.235002
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发表时间：
2019-11-15
影响因子：
4
通讯作者：
Kraft, Claudine
中科院分区：
文献类型：
--
作者：
Hollenstein, David M.;Gomez-Sanchez, Rubeprimen;Kraft, Claudine
自噬是由吞噬细胞组装位点（PAS）的形成启动的，PAS是自噬体的前体。在哺乳动物中，自噬体形成位点在内质网（ER）的专门亚结构域中遍及胞质溶胶形成。在酵母中，PAS也在ER附近产生，但总是在液泡附近。PAS如何锚定到液泡和这种定位的功能意义是未知的。在这里，我们研究了PAS-空泡连接在酿酒酵母（Saccharomyces cerevisiae）中的作用。我们发现，Vac 8构成了一个液泡系链，通过PAS组分Atg 13在整个自噬体生物发生过程中将PAS稳定地锚定在液泡上。S.缺乏Vac 8的酿酒酵母显示出低效的自噬体-空泡融合，并且形成更少和更小的自噬体，其通常远离空泡定位。因此，由Vac 8建立的稳定PAS-空泡连接在ER和空泡之间为自噬体生物发生创造了有限的空间，并允许自噬体形成和自噬体-空泡融合的空间协调。这些发现揭示了在空泡处自噬体形成的空间调节是有效的大量自噬所必需的。
Autophagy is initiated by the formation of a phagophore assembly site (PAS), the precursor of autophagosomes. In mammals, autophagosome formation sites form throughout the cytosol in specialized subdomains of the endoplasmic reticulum (ER). In yeast, the PAS is also generated close to the ER, but always in the vicinity of the vacuole. How the PAS is anchored to the vacuole and the functional significance of this localization are unknown. Here, we investigated the role of the PAS-vacuole connection for bulk autophagy in the yeast Saccharomyces cerevisiae. We show that Vac8 constitutes a vacuolar tether that stably anchors the PAS to the vacuole throughout autophagosome biogenesis via the PAS component Atg13. S. cerevisiae lacking Vac8 show inefficient autophagosome-vacuole fusion, and form fewer and smaller autophagosomes that often localize away from the vacuole. Thus, the stable PAS-vacuole connection established by Vac8 creates a confined space for autophagosome biogenesis between the ER and the vacuole, and allows spatial coordination of autophagosome formation and autophagosome-vacuole fusion. These findings reveal that the spatial regulation of autophagosome formation at the vacuole is required for efficient bulk autophagy.