Vac8 spatially confines autophagosome formation at the vacuole in S. cerevisiae

被引:56
作者
Hollenstein, David M. [1 ]
Gomez-Sanchez, Rubeprimen [5 ]
Ciftci, Akif [2 ,3 ]
Kriegenburg, Franziska [2 ]
Mari, Muriel [5 ]
Torggler, Raffaela [2 ,3 ]
Licheva, Mariya [2 ,3 ]
Reggiori, Fulvio [5 ]
Kraft, Claudine [2 ,4 ]
机构
[1] Univ Vienna, Vienna BioCtr, Max Perutz Labs, Dept Biochem & Cell Biol, Dr Bohr Gasse 9, A-1030 Vienna, Austria
[2] Univ Freiburg, Fac Med, ZBMZ, Inst Biochem & Mol Biol, D-79104 Freiburg, Germany
[3] Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany
[4] Univ Freiburg, CIBSS, Freiburg, Germany
[5] Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Sci Cells & Syst, NL-9713 AV Groningen, Netherlands
基金
奥地利科学基金会; 欧洲研究理事会; 欧盟地平线“2020”;
关键词
Autophagy; Vac8; Autophagosome; Phagophore assembly site; PAS; SACCHAROMYCES-CEREVISIAE; ATG1; KINASE; ENDOPLASMIC-RETICULUM; NONSPECIFIC AUTOPHAGY; PROTEIN INTERACTIONS; SELECTIVE AUTOPHAGY; COMPLEX; INITIATION; CYTOPLASM; NUCLEUS;
D O I
10.1242/jcs.235002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:16
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