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J Cell Sci. 2019 Nov 14;132(22). pii: jcs235002. doi: 10.1242/jcs.235002.

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

Author information

1
Department of Biochemistry and Cell Biology, Max Perutz Labs, University of Vienna, Vienna BioCenter, Dr. Bohr-Gasse 9, 1030 Vienna, Austria.
2
Department of Biomedical Sciences of Cells & Systems, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
3
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
4
Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
5
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany kraft@biochemie.uni-freiburg.de.
6
CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg.

Abstract

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.

KEYWORDS:

Autophagosome; Autophagy; PAS; Phagophore assembly site; Vac8

PMID:
31649143
DOI:
10.1242/jcs.235002
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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