Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation

Mao, Kai; Chew, Leon H.; Inoue-Aono, Yuko; Cheong, Heesun; Nair, Usha; Popelka, Hana; Yip, Calvin K.; Klionsky, Daniel J.

doi:10.1073/pnas.1300064110

Cited by 79 publications

(98 citation statements)

References 49 publications

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“…Notably, we have shown that this Atg29 domain serves as a phospho-regulatory domain that is highly phosphorylated during autophagy induction and further associates with the PAS organizer Atg11. 31 Atg11 is another scaffold protein consisting of primarily coiled-coil domains similar to Atg17. Future work will focus on further defining how phosphorylation affects the strength and specificity of the Atg17-Atg29 interaction.…”

Section: Discussionmentioning

confidence: 99%

“…29 During nonstarvation conditions, this assembly utilizes the Atg11 protein to promote its localization to the PAS. 30,31 As one of the first set of Atg proteins to be targeted to the PAS upon autophagy induction, the Atg17-Atg31-Atg29 subcomplex (hereafter Atg17-Atg31-Atg29), along with Atg11, are thought to serve as molecular scaffolds to organize the PAS. 22,30,31 Support for this proposed function has arisen from recent structural studies of Atg17-Atg31-Atg29, which revealed that this subcomplex adopts a highly extended "Sshaped" dimeric architecture.…”

Section: Introductionmentioning

confidence: 99%

“…30,31 As one of the first set of Atg proteins to be targeted to the PAS upon autophagy induction, the Atg17-Atg31-Atg29 subcomplex (hereafter Atg17-Atg31-Atg29), along with Atg11, are thought to serve as molecular scaffolds to organize the PAS. 22,30,31 Support for this proposed function has arisen from recent structural studies of Atg17-Atg31-Atg29, which revealed that this subcomplex adopts a highly extended "Sshaped" dimeric architecture. 22,32 Each Atg17 protomer associates with a heterodimer of Atg31-Atg29, and dimerization of Atg17 results in an assembly with a 2:2:2 stoichiometry of the 3 components.…”

Section: Introductionmentioning

confidence: 99%

“…Atg31 and Atg29 likely serve regulatory functions as both proteins are phosphorylated upon autophagy activation. 29,31 Indeed, the C terminus of Atg29 constitutes a regulatory phosphopeptide that modulates Atg29 association with Atg11 in a phosphorylation-dependent manner. 31 Despite recent progress in understanding the function of the Atg1 complex, the assembly mechanism of this complex has not been fully defined.…”

Section: Introductionmentioning

confidence: 99%

“…29,31 Indeed, the C terminus of Atg29 constitutes a regulatory phosphopeptide that modulates Atg29 association with Atg11 in a phosphorylation-dependent manner. 31 Despite recent progress in understanding the function of the Atg1 complex, the assembly mechanism of this complex has not been fully defined. The structure of the Lachancea thermotolerans Atg17-Atg31-Atg29 subcomplex has provided a first glimpse into a core portion of the Atg1 complex.…”

Section: Introductionmentioning

confidence: 99%

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Molecular interactions of theSaccharomyces cerevisiaeAtg1 complex provide insights into assembly and regulatory mechanisms

Chew¹,

Liu³

et al. 2015

Autophagy

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(2015) Molecular interactions of the Saccharomyces cerevisiae Atg1 complex provide insights into assembly and regulatory mechanisms, Autophagy, 11:6, 891-905, DOI: 10.1080/15548627.2015 The Atg1 complex, which contains 5 major subunits: Atg1, Atg13, Atg17, Atg29, and Atg31, regulates the induction of autophagy and autophagosome formation. To gain a better understanding of the overall architecture and assembly mechanism of this essential autophagy regulatory complex, we have reconstituted a core assembly of the Saccharomyces cerevisiae Atg1 complex composed of full-length Atg17, Atg29, and Atg31, along with the C-terminal domains of Atg1 (Atg1 [CTD]) and Atg13 (Atg13 [CTD]). Using chemical-crosslinking coupled with mass spectrometry (CXMS) analysis we systematically mapped the intersubunit interaction interfaces within this complex. Our data revealed that the intrinsically unstructured C-terminal domain of Atg29 interacts directly with Atg17, whereas Atg17 interacts with Atg13 in 2 distinct intrinsically unstructured regions, including a previously unknown motif that encompasses several putative phosphorylation sites. The Atg1[CTD] crosslinks exclusively to the Atg13[CTD] and does not appear to make direct contact with the Atg17-Atg31-Atg29 scaffold. Finally, single-particle electron microscopy analysis revealed that both the Atg13[CTD] and Atg1 [CTD] localize to the tip regions of Atg17-Atg31-Atg29 and do not alter the distinct curvature of this scaffolding subcomplex. This work provides a comprehensive understanding of the subunit interactions in the fully assembled Atg1 core complex, and uncovers the potential role of intrinsically disordered regions in regulating complex integrity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular interactions of theSaccharomyces cerevisiaeAtg1 complex provide insights into assembly and regulatory mechanisms

Chew¹,

Liu³

et al. 2015

Autophagy

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On the edge of degradation: Autophagy regulation by RNA decay

Delorme-Axford

Klionsky

2018

WIREs RNA

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Cells must dynamically adapt to altered environmental conditions, particularly during times of stress, to ensure their ability to function effectively and survive. The macroautophagy/autophagy pathway is highly conserved across eukaryotic cells and promotes cell survival during stressful conditions. In general, basal autophagy occurs at a low level to sustain cellular homeostasis and metabolism. However, autophagy is robustly upregulated in response to nutrient deprivation, pathogen infection and increased accumulation of potentially toxic protein aggregates and superfluous organelles. Within the cell, RNA decay maintains quality control to remove aberrant transcripts and regulate appropriate levels of gene expression. Recent evidence has identified components of the cellular mRNA decay machinery as novel regulators of autophagy. Here, we review current findings that demonstrate how autophagy is modulated through RNA decay. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability K E Y W O R D S Dcp2, DDX6, Dhh1, mRNA decay, RNA degradation, vacuole, Xrn1/XRN1, yeast 1 | INTRODUCTION 1.1 | OverviewWhen encountering altered environments and fluctuating nutrient conditions, cells must respond and adapt through mechanisms that support their survival. Autophagy is a precisely controlled catabolic process of cellular "self-eating" that is highly conserved across eukaryotes (from yeast to human). Starvation, pathogen infection and/or the accumulation of damaged or superfluous organelles can activate the autophagy pathway, which enables eukaryotic cells to function and survive amid stress conditions. Autophagy also removes harmful cellular material, while at the same time providing a source of macromolecules to sustain cellular metabolism during low-energy periods. The de novo formation of the sequestering phagophore, which matures into a double-membrane autophagosome is the characteristic morphological feature of autophagy. At present, 42 autophagy-related (ATG) genes have been identified in fungi; many of these genes have homologs or at least functional counterparts in higher eukaryotes. Autophagy is primarily a degradative pathway requiring the vacuole (in yeast or plants) or lysosomes (in metazoans) for the breakdown of sequestered cargo. However, the biosynthetic cytoplasm-to-vacuole targeting (Cvt) pathway utilizes most of Abbreviations: ATG, autophagy-related; CPA, cleavage and polyadenylation; Cvt, cytoplasm-to-vacuole targeting; GABARAP, GABA type A receptorassociated protein; MAP1LC3/ LC3, microtubule associated protein 1 light chain 3; miRNA, microRNA; mRNA, messenger RNA; MTOR, mechanistic target of rapamycin kinase;

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Biodiversity of autolytic ability in flocculent Saccharomyces cerevisiae strains suitable for traditional sparkling wine fermentation

Perpetuini

Gianvito

Arfelli

et al. 2016

Yeast

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Yeasts involved in secondary fermentation of traditional sparkling wines should show specific characteristics, such as flocculation capacity and autolysis. Recently it has been postulated that autophagy may contribute to the outcome of autolysis. In this study, 28 flocculent wine Saccahromyces cerevisiae strains characterized by different flocculation degrees were studied for their autolytic and autophagic activities. Autolysis was monitored in synthetic medium through the determination of amino acid nitrogen and total proteins released. At the same time, novel primer sets were developed to determine the expression of the genes ATG1, ATG17 and ATG29. Twelve strains were selected on the basis of their autolytic rate and ATG gene expressions in synthetic medium and were inoculated in a base wine. After 30, 60 and 180 days the autolytic process and ATG gene expressions were evaluated. The obtained data showed that autolysis and ATG gene expressions differed among strains and were independent of the degree of flocculation. This biodiversity could be exploited to select new starter stains to improve sparkling wine production.

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Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation

Cited by 79 publications

References 49 publications

Molecular interactions of theSaccharomyces cerevisiaeAtg1 complex provide insights into assembly and regulatory mechanisms

Molecular interactions of theSaccharomyces cerevisiaeAtg1 complex provide insights into assembly and regulatory mechanisms

On the edge of degradation: Autophagy regulation by RNA decay

Biodiversity of autolytic ability in flocculent Saccharomyces cerevisiae strains suitable for traditional sparkling wine fermentation

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