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

doi:10.1128/MCB.00079-13

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Role of Membrane Association and Atg14-Dependent Phosphorylation in Beclin-1-Mediated Autophagy

Journal article

Peer reviewed

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 and Richard J Youle

Molecular and cellular biology, Vol.33(18), pp.3675-3688

09/2013

DOI: 10.1128/MCB.00079-13

PMCID: PMC3753860

PMID: 23878393

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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.

Details

Title: Subtitle: Role of Membrane Association and Atg14-Dependent Phosphorylation in Beclin-1-Mediated Autophagy
Creators: Adam I Fogel - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Brian J Dlouhy - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Chunxin Wang - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Seung-Wook Ryu - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Albert Neutzner - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Samuel A Hasson - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Dionisia P Sideris - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Hagai Abeliovich - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Richard J Youle - Biochemistry Section, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.33(18), pp.3675-3688
DOI: 10.1128/MCB.00079-13
PMID: 23878393
PMCID: PMC3753860
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Publisher: American Society for Microbiology; 1752 N St., N.W., Washington, DC
Language: English
Date published: 09/2013
Academic Unit: Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984040347802771

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