Molecular interactions of the<i>Saccharomyces cerevisiae</i>Atg1 complex provide insights into assembly and regulatory mechanisms

Chew, Leon H.; Lu, Shan; Liu, Xu; Li, Franco Kk; Yu, Angela; Klionsky, Daniel J.; Dong, Meng; Yip, Calvin K.

doi:10.1080/15548627.2015.1040972

Cited by 33 publications

(36 citation statements)

References 54 publications

(105 reference statements)

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“…This disease may be treatable via an autophagic signal, and a few drugs that can regulate autophagy have been identified. Autophagy is not only protective, but it may also have an impaired impact on the cell; however, there is limited clinical data to demonstrate its curative role, and currently the treatment of cardiovascular disease generally involves the downregulation of autophagy (45).…”

Section: Discussionmentioning

confidence: 99%

Role of autophagy in advanced atherosclerosis

Zhu

Fan

Zhang

et al. 2017

Molecular Medicine Reports

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Abstract. Atherosclerosis (AS) remains the leading cause for global cardiovascular disease morbidity and mortality, and a major cause of cardiopathy, myocardial infarction and peripheral vascular diseases. Macrophages serve a critical role in atherosclerotic plaque stabilization and rupture, and the selective removal of macrophages may be beneficial in improving plaque stability. Autophagy is a process of self-feeding, during which cytoplasmic proteins or organelles are packaged into vesicles and fused with the lysosome to form an autophagosome. The newly formed autophagosome can degrade internalized proteins, and this process may be used to serve the metabolic and self-renewal requirements of the cell. Autophagy serves an important role in maintaining cell homeostasis and promoting cell survival, and therefore an imbalance in autophagy is closely associated with multiple diseases. Contents1. Introduction 2. The molecular mechanism of autophagy 3. Autophagy in the vascular system 4. Autophagy in AS 5. Conclusions IntroductionAutophagy is a process of cellular repair and survival, during which cytoplasmic components are sequestered into double-membrane vesicles. Previous research has revealed that autophagy is stimulated in advanced atherosclerotic plaques by oxidized lipids, inflammation and metabolic stress (1). Autophagy is beneficial in promoting cellular recovery in adverse environments; it is also valuable in inhibiting apoptosis. In advanced atherosclerosis (AS), macrophage apoptosis, together with defective phagocytic clearance of the apoptotic cells, promotes plaque necrosis, which results in acute atherothrombotic cardiovascular events (2). Basal autophagy is beneficial in early AS, however a detrimental effect is observed in advanced AS plaques (3); autophagy is capable of protecting cells from oxidative stress via the degradation of damaged intracellular material; however, excessively stimulated autophagic activity may result in significant destruction of the cytosol (1). The latter scenario leads to programmed cell death and may cause vascular endothelial cell (VEC) death, which results in plaque destabilization. Endothelial injury or death represents a predominant mechanism of acute clinical events, due to the promotion of lesional thromboses (4). Furthermore, insufficient autophagic activity also reduces free cholesterol and apolipoprotein A-I (5), and this decreases the amount of high-density lipoprotein. Insufficient and excessive autophagy of VECs are therefore both injurious, and the regulation of autophagic homeostasis may be important in the treatment of AS. The molecular mechanism of autophagyWhen Ashford and Porter (6) perfused rat livers with glucagon, they discovered a large increase in the number of cellular lysosomes. This phenomenon of self-feeding was referred to as autophagy. This process involves the packaging of cytoplasmic proteins or organelles into vesicles, followed by lysosomal fusion, to form an autophagic lysosome; a cellular event which aids in metabolism and in the renewal...

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Section: Discussionmentioning

confidence: 99%

Role of autophagy in advanced atherosclerosis

Zhu

Fan

Zhang

et al. 2017

Molecular Medicine Reports

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“…In the cell, the Atg17-Atg31-Atg29 ternary subcomplex is present as a dimer, and the two crescents of Atg17 are assembled as to form an “S” shape [38, 79]. Atg31 binds to Atg17 via an α-helix in the C-terminal region, but interacts with Atg29 via a β-sandwich at the N terminus; based on chemical-crosslinking coupled with mass spectrometry, Atg17 and Atg29 also appear to directly interact [85]. Atg17 may also interact with the Atg1-Atg13 complex via Atg11, a scaffold protein that binds to several autophagy-related proteins including Atg1, and Atg29.…”

Section: Structure Function and Modification Of The Core Autophagmentioning

confidence: 99%

An overview of macroautophagy in yeast

Wen

Klionsky

2016

Journal of Molecular Biology

229

188

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Macroautophagy is an evolutionarily conserved dynamic pathway that functions primarily in a degradative manner. A basal level of macroautophagy occurs constitutively, but this process can be further induced in response to various types of stress including starvation, hypoxia and hormonal stimuli. The general principle behind macroautophagy is that cytoplasmic contents can be sequestered within a transient double-membrane organelle, an autophagosome, which subsequently fuses with a lysosome or vacuole (in mammals, or yeast and plants, respectively), allowing degradation of the cargo followed by recycling of the resulting macromolecules. Through this basic mechanism, macroautophagy has a critical role in cellular homeostasis; however, either insufficient or excessive macroautophagy can seriously compromise cell physiology, and thus it needs to be properly regulated. In fact, a wide range of diseases is associated with dysregulation of macroautophagy. There has been substantial progress in understanding the regulation and molecular mechanisms of macroautophagy in different organisms; however, many questions concerning some most fundamental aspects of macroautophagy still remain unresolved. In this review, we summarize current knowledge about macroautophagy mainly in yeast, including the mechanism of autophagosome biogenesis, the function of the core macroautophagic machinery, the regulation of macroautophagy, and the process of cargo recognition in selective macroautophagy, with the goal of providing insights into some of the key unanswered questions in this field.

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“…Subsequent EM analysis of the Atg17-31-29 complex established that the Atg13 subunit bound to the tips of the S-shape (13). The importance of this is that Atg13 is the bridge to the catalytic Atg1 subunit.…”

Section: The Core Machinery Of Autophagymentioning

confidence: 99%

Next-generation electron microscopy in autophagy research

Hurley

Nogales

2016

Current Opinion in Structural Biology

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Autophagy is the process whereby cytosol, organelles, and inclusions are taken up in a double-membrane vesicle known as the autophagosome, and transported to the lysosome for destruction and recycling. Electron microscopy (EM) led to the discovery of autophagy in the 1950s and has been a central part of its characterization ever since. New capabilities in single particle EM studies of the autophagy machinery are beginning to provide exciting insights into the mechanisms of autophagosome initiation, growth, and substrate targeting. These include EM structures at various resolutions of part of the Atg1 protein kinase complex and all of the class III phosphatidylinositol 3-phosphate complex I that initiate autophagy; the mTORC1 complex that regulates autophagy initiation; the Ape1 particle, a major substrate for selective autophagy in yeast; and p62, a mammalian selective autophagy adaptors. Equally exciting are the prospects for increased resolution and insight into autophagosome formation in cells from advances in cryo-EM tomography and focused ion beam-scanning electron microscopy (FIB-SEM). This review considers recent accomplishments, prospects for progress, and remaining obstacles that still need to be overcome.

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

Cited by 33 publications

References 54 publications

Role of autophagy in advanced atherosclerosis

Role of autophagy in advanced atherosclerosis

An overview of macroautophagy in yeast

Next-generation electron microscopy in autophagy research

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