Atg19 Mediates a Dual Interaction Cargo Sorting Mechanism in Selective Autophagy

Chang, Chen‐Ming; Huang, Wei‐Pang

doi:10.1091/mbc.e06-08-0683

Cited by 56 publications

(58 citation statements)

References 42 publications

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“…As expected (Farre et al, 2007), ⌬atg1 was affected in both Cvt-and autophagy-dependent maturation of Ape1, and ⌬atg11 was only impaired in the Cvt-dependent maturation of Ape1. However, in contrast to S. cerevisiae, where Atg8 is essential for the Cvt pathway and only partially required for autophagy (Kirisako et al, 1999;Abeliovich et al, 2000;Chang and Huang, 2007), PpAtg8 was essential for both processes (Supplemental Figure S4B). These results (Supplemental Figure S4, A and B) show that PpAtg8 is essential for all autophagyrelated pathways and is not redundant with Atg11 in bridging the receptor-cargo complexes with the PAS.…”

Section: Dual Interaction Of Atg30 With Atg11 and Atg17 Is Required Tmentioning

confidence: 95%

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Peroxisome Size Provides Insights into the Function of Autophagy-related Proteins

Nazarko

Farré

Subramani

2009

MBoC

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Autophagy is a major pathway of intracellular degradation mediated by formation of autophagosomes. Recently, autophagy was implicated in the degradation of intracellular bacteria, whose size often exceeds the capacity of normal autophagosomes. However, the adaptations of the autophagic machinery for sequestration of large cargos were unknown. Here we developed a yeast model system to study the effect of cargo size on the requirement of autophagy-related (Atg) proteins. We controlled the size of peroxisomes before their turnover by pexophagy, the selective autophagy of peroxisomes, and found that peroxisome size determines the requirement of Atg11 and Atg26. Small peroxisomes can be degraded without these proteins. However, Atg26 becomes essential for degradation of medium peroxisomes. Additionally, the pexophagy-specific phagophore assembly site, organized by the dual interaction of Atg30 with functionally active Atg11 and Atg17, becomes essential for degradation of large peroxisomes. In contrast, Atg28 is partially required for all autophagy-related pathways independent of cargo size, suggesting it is a component of the core autophagic machinery. As a rule, the larger the cargo, the more cargo-specific Atg proteins become essential for its sequestration. INTRODUCTIONMacroautophagy (hereafter autophagy) is a conservative eukaryotic pathway for the degradation of intracellular material in the lysosome/vacuole via its sequestration by doublemembrane vesicles called autophagosomes. Autophagy has been implicated in many physiological processes and human diseases (Huang and Klionsky, 2007;Rubinsztein et al., 2007;Mizushima et al., 2008). It is mainly a nonselective process sequestering a random portion of cytoplasm under starvation conditions. However, under certain conditions protein complexes, organelles and intracellular pathogens are selectively removed from the cytosol by specialized autophagy-related pathways. For example, the cytoplasm-tovacuole targeting (Cvt) pathway selectively delivers certain vacuolar resident hydrolases under vegetative conditions (Stromhaug and Klionsky, 2003;Farre et al., 2007), macropexophagy (hereafter pexophagy) ensures selective turnover of peroxisomes under peroxisome repression conditions (Dunn et al., 2005;Monastyrska and Klionsky, 2006;Sakai et al., 2006), and xenophagy selectively disposes microbes that invade cells during infection (Levine and Deretic, 2007;Schmid and Munz, 2007).Irrespective of the material being degraded by autophagyrelated pathways, multiple steps are required to sequester it from the cytosol in double-membrane vesicles. These include induction of the particular pathway, cargo selection and packaging, nucleation of vesicle formation, vesicle expansion and completion, retrieval of autophagic machinery components, fusion of completed vesicles with the lysosome/vacuole, breakdown of the single-membrane vesicle and its cargo, and transport of liberated amino acids and lipids to the cytosol for reuse (Klionsky, 2005;. To date, 32 autophagy-related (Atg) protein...

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Section: Dual Interaction Of Atg30 With Atg11 and Atg17 Is Required Tmentioning

confidence: 95%

“…In growing cells Atg11 plays a major role in bridging the Ape1-Atg19 complex with the PAS. However, upon nitrogen starvation, the increased levels of Atg8 cause a partial bypass of the Atg11-dependent step (Chang and Huang, 2007). In P. pastoris Atg30 also interacts with Atg11 (Farre et al, 2008).…”

mentioning

confidence: 99%

Peroxisome Size Provides Insights into the Function of Autophagy-related Proteins

Nazarko

Farré

Subramani

2009

MBoC

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“…Experiments in which the amount of Atg8 is clamped at levels lower than that normally generated during autophagy induction indicate that the amount of this protein correlates with the size of the autophagosome (Xie et al 2008). Atg8 that lines the concave side of the phagophore also plays a role in cargo recognition during selective types of autophagy by binding the receptors used in the Cvt pathway, pexophagy, and mitophagy (Shintani et al 2002;Chang and Huang 2007;Mijaljica et al 2012;Motley et al 2012). X-ray crystallography, combined with NMR, has revealed that a hydrophobic pocket in Atg8 interacts with the Atg8-interacting motif (AIM, or, with regard to the mammalian homolog, an LC3-interacting region, LIR) in Atg19, providing insight into the mechanism of selective cargo recognition (Noda et al 2008).…”

Section: Macroautophagymentioning

confidence: 99%

Autophagic Processes in Yeast: Mechanism, Machinery and Regulation

2013

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Autophagy refers to a group of processes that involve degradation of cytoplasmic components including cytosol, macromolecular complexes, and organelles, within the vacuole or the lysosome of higher eukaryotes. The various types of autophagy have attracted increasing attention for at least two reasons. First, autophagy provides a compelling example of dynamic rearrangements of subcellular membranes involving issues of protein trafficking and organelle identity, and thus it is fascinating for researchers interested in questions pertinent to basic cell biology. Second, autophagy plays a central role in normal development and cell homeostasis, and, as a result, autophagic dysfunctions are associated with a range of illnesses including cancer, diabetes, myopathies, some types of neurodegeneration, and liver and heart diseases. That said, this review focuses on autophagy in yeast. Many aspects of autophagy are conserved from yeast to human; in particular, this applies to the gene products mediating these pathways as well as some of the signaling cascades regulating it, so that the information we relate is relevant to higher eukaryotes. Indeed, as with many cellular pathways, the initial molecular insights were made possible due to genetic studies in Saccharomyces cerevisiae and other fungi. TABLE OF CONTENTS Abstract 341Introduction 342

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“…The C-terminal region of Atg19, which is essential for interaction with Atg8, contains hydrophobic residues homologous to that in LRS (WXXL sequence), although there is no overall sequence homology between them. 12,22,23 Atg8 might recognize Atg19 in a molecular mechanism similar to the LC3-p62 interaction.…”

Section: Other Cargo Recognition By the Atg8 Familymentioning

confidence: 99%

Selective turnover of p62/A170/SQSTM1 by autophagy

Ichimura

Kominami²,

Tanaka³

et al. 2008

Autophagy

211

157

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Loss of autophagy causes liver injury, cardiomyopathy and neurodegeneration, associated with the formation of ubiquitinpositive inclusion bodies. However, the pathogenic mechanism and molecular machinery involved in inclusion formation are not fully understood. We recently identified a ubiquitin-binding protein, p62/A170/SQSTM1, as a molecule involved in inclusion formation. p62 interacts with LC3 which regulates autophagosome formation, through an 11 amino acid sequence rich in acidic and hydrophobic residues, named the LC3-recognition sequence (LRS), and the LC3-p62 complex is degraded by autophagy. Furthermore, structural analysis reveals an interaction of Trp-340 and Leu-343 of p62 with different hydrophobic pockets in the ubiquitin-fold of LC3. p62 mutants, defective in binding the LRS, escape efficient turnover by autophagy, forming ubiquitin-and p62-positive inclusions. Importantly, such ubiquitin-and p62-positive inclusions are identified in various human diseases, implying the involvement of autophagy in their pathogenic mechanisms. Our reports identify an important role for autophagy in the selective turnover of p62, and demonstrate that in addition to the essential role of LC3 in autophagosome formation, LC3 is also involved in sorting autophagy-specific substrate(s).

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Atg19 Mediates a Dual Interaction Cargo Sorting Mechanism in Selective Autophagy

Cited by 56 publications

References 42 publications

Peroxisome Size Provides Insights into the Function of Autophagy-related Proteins

Peroxisome Size Provides Insights into the Function of Autophagy-related Proteins

Autophagic Processes in Yeast: Mechanism, Machinery and Regulation

Selective turnover of p62/A170/SQSTM1 by autophagy

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