Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy

Adam I. Fogel, Brian J. Dlouhy, Chunxin Wang, Seung Wook Ryu, Albert Neutzner, Samuel A. Hasson, Dionisia P. Sideris, Hagai Abeliovich, Richard J. Youle*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

During autophagy, a double membrane envelops cellular material for trafficking to the lysosome. Human beclin-1 and its yeast homologue, Atg6/Vps30, are scaffold proteins bound in a lipid kinase complex with multiple cellular functions, including autophagy. Several different Atg6 complexes exist, with an autophagy-specific form containing Atg14. However, the roles of Atg14 and beclin-1 in the activation of this complex remain unclear. We here addressed the mechanism of beclin-1 complex activation and reveal two critical steps in this pathway. First, we identified a unique domain in beclin-1, conserved in the yeast homologue Atg6, which is involved in membrane association and, unexpectedly, controls autophagosome size and number in yeast. Second, we demonstrated that human Atg14 is critical in controlling an autophagy-dependent phosphorylation of beclin-1. We map these novel phosphorylation sites to serines 90 and 93 and demonstrate that phosphorylation at these sites is necessary for maximal autophagy. These results help clarify the mechanism of beclin-1 and Atg14 during autophagy.

Original languageAmerican English
Pages (from-to)3675-3688
Number of pages14
JournalMolecular and Cellular Biology
Volume33
Issue number18
DOIs
StatePublished - 2013

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