scholarly journals The molecular basis of selective autophagy

2012 ◽  
Vol 34 (2) ◽  
pp. 24-30 ◽  
Author(s):  
Doris Popovic ◽  
Ivan Dikic
Keyword(s):  
Molecular Basis ◽  
Membrane Vesicles ◽  
Degradation Process ◽  
Degradation Pathway ◽  
Selective Autophagy ◽  
Intracellular Degradation ◽  
Selective Degradation ◽  
Evolutionarily Conserved ◽  
The Family ◽  
Cellular Components

Autophagy is an evolutionarily conserved intracellular degradation process, through which large cellular cargos are sequestered into double-membrane vesicles (autophagosomes) and delivered to the lysosome. Starvation-induced autophagy represents a general non-selective degradation pathway that breaks down cellular components for energy replenishment. Alternatively, selective autophagy targets specific organelles, protein aggregates or invading pathogens that need to be precisely removed from the cell during development or pathogenic infection. Selective autophagy receptors noncovalently bind to the family of ATG8 modifiers and can be controlled by post-translational protein modifications, including ubiquitination and phosphorylation. In this article, we review recent advances in our understanding of the molecular basis of cargo selection in autophagy.

scholarly journals The Role of Chaperone-Mediated Autophagy in Hepatitis C Virus-Induced Pathogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Chieko Matsui ◽  
Putu Yuliandari ◽  
Lin Deng ◽  
Takayuki Abe ◽  
Ikuo Shoji
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Degradation Process ◽  
Degradation Pathway ◽  
Hepatocyte Nuclear Factor ◽  
Selective Degradation ◽  
Substrate Protein ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Chaperone Mediated Autophagy

Lysosome incorporate and degrade proteins in a process known as autophagy. There are three types of autophagy; macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Although autophagy is considered a nonselective degradation process, CMA is known as a selective degradation pathway. All proteins internalized in the lysosome via CMA contain a pentapeptide KFERQ-motif, also known as a CMA-targeting motif, which is necessary for selectivity. CMA directly delivers a substrate protein into the lysosome lumen using the cytosolic chaperone HSC70 and the lysosomal receptor LAMP-2A for degradation. Hepatitis C virus (HCV) NS5A protein interacts with hepatocyte-nuclear factor 1α (HNF-1α) together with HSC70 and promotes the lysosomal degradation of HNF-1α via CMA, resulting in HCV-induced pathogenesis. HCV NS5A promotes recruitment of HSC70 to the substrate protein HNF-1α. HCV NS5A plays a crucial role in HCV-induced CMA. Further investigations of HCV NS5A-interacting proteins containing CMA-targeting motifs may help to elucidate HCV-induced pathogenesis.

scholarly journals Recent Advances in Single-Particle Electron Microscopic Analysis of Autophagy Degradation Machinery

2020 ◽  
Vol 21 (21) ◽  
pp. 8051
Author(s):  
Yiu Wing Sunny Cheung ◽  
Sung-Eun Nam ◽  
Calvin K. Yip
Keyword(s):  
Single Particle ◽  
Membrane Vesicle ◽  
Microscopic Analysis ◽  
Degradation Process ◽  
Electron Microscopic ◽  
Major Pathway ◽  
Selective Autophagy ◽  
Selective Degradation ◽  
The Core ◽  
Atg Proteins

Macroautophagy (also known as autophagy) is a major pathway for selective degradation of misfolded/aggregated proteins and damaged organelles and non-selective degradation of cytoplasmic constituents for the generation of power during nutrient deprivation. The multi-step degradation process, from sequestering cytoplasmic cargo into the double-membrane vesicle termed autophagosome to the delivery of the autophagosome to the lysosome or lytic vacuole for breakdown, is mediated by the core autophagy machinery composed of multiple Atg proteins, as well as the divergent sequence family of selective autophagy receptors. Single-particle electron microscopy (EM) is a molecular imaging approach that has become an increasingly important tool in the structural characterization of proteins and macromolecular complexes. This article summarizes the contributions single-particle EM have made in advancing our understanding of the core autophagy machinery and selective autophagy receptors. We also discuss current technical challenges and roadblocks, as well as look into the future of single-particle EM in autophagy research.

LncRNAs as Therapeutic Targets for Autophagy-involved Cardiovascular Diseases: A Review of Molecular Mechanism and Therapy Strategy

2020 ◽  
Vol 27 ◽  
Author(s):  
Lihui Jin ◽  
Nanchao Hong ◽  
Xuefeng Ai ◽  
Jing Wang ◽  
Zhuoyan Li ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Noncoding Rna ◽  
Environmental Variability ◽  
Current Knowledge ◽  
Degradation Process ◽  
Rna Sequences ◽  
Intracellular Degradation ◽  
Therapy Strategy ◽  
Evolutionarily Conserved ◽  
Recent Developments

Background: Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. The concept of precision medicine in CVD therapy today requires incorporation of individual genetic and environmental variability to achieve personalized disease prevention and tailored treatment. Autophagy, an evolutionarily conserved intracellular degradation process, has been demonstrated to be essential in the pathogenesis of various CVDs. Nonetheless, there have been no effective treatments for autophagy-involved CVDs. Long noncoding RNAs (lncRNAs) are noncoding RNA sequences that play versatile roles in autophagy regulation, but much needs to be explored about the relationship between lncRNAs and autophagy-involved CVDs. Summary: Increasing evidence has shown that lncRNAs contribute considerably to modulate autophagy in the context of CVDs. In this review, we first summarize the current knowledge of the role lncRNAs play in cardiovascular autophagy and autophagy-involved CVDs. Then recent developments of antisense oligonucleotides (ASOs) designed to target lncRNAs to specifically modulate autophagy in diseased hearts and vessels are discussed, focusing primarily on structure-activity relationships of distinct chemical modifications and relevant clinical trials. Perspective: ASOs are promising in cardiovascular drug innovation. We hope that future studies of lncRNA-based therapies would overcome existing technical limitations, and help people who suffering from autophagy-involved CVDs.

scholarly journals Cargo Recognition and Function of Selective Autophagy Receptors in Plants

2021 ◽  
Vol 22 (3) ◽  
pp. 1013
Author(s):  
Shuwei Luo ◽  
Xifeng Li ◽  
Yan Zhang ◽  
Yunting Fu ◽  
Baofang Fan ◽  
...  
Keyword(s):  
Cellular Response ◽  
Plant Responses ◽  
Biological Functions ◽  
Biotic And Abiotic Stresses ◽  
Selective Autophagy ◽  
Evolutionarily Conserved ◽  
Autophagic Degradation ◽  
Species Specific ◽  
And Function ◽  
Cellular Components

Autophagy is a major quality control system for degradation of unwanted or damaged cytoplasmic components to promote cellular homeostasis. Although non-selective bulk degradation of cytoplasm by autophagy plays a role during cellular response to nutrient deprivation, the broad roles of autophagy are primarily mediated by selective clearance of specifically targeted components. Selective autophagy relies on cargo receptors that recognize targeted components and recruit them to autophagosomes through interaction with lapidated autophagy-related protein 8 (ATG8) family proteins anchored in the membrane of the forming autophagosomes. In mammals and yeast, a large collection of selective autophagy receptors have been identified that mediate the selective autophagic degradation of organelles, aggregation-prone misfolded proteins and other unwanted or nonnative proteins. A substantial number of selective autophagy receptors have also been identified and functionally characterized in plants. Some of the autophagy receptors in plants are evolutionarily conserved with homologs in other types of organisms, while a majority of them are plant-specific or plant species-specific. Plant selective autophagy receptors mediate autophagic degradation of not only misfolded, nonactive and otherwise unwanted cellular components but also regulatory and signaling factors and play critical roles in plant responses to a broad spectrum of biotic and abiotic stresses. In this review, we summarize the research on selective autophagy in plants, with an emphasis on the cargo recognition and the biological functions of plant selective autophagy receptors.

scholarly journals Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Yuan Li ◽  
Shaogui Wang ◽  
Hong-Min Ni ◽  
Heqing Huang ◽  
Wen-Xing Ding
Keyword(s):  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Degradation Pathway ◽  
Protective Mechanism ◽  
Intracellular Degradation ◽  
Injury Mechanisms ◽  
Evolutionarily Conserved

Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy.

scholarly journals The Role of Autophagy and Autophagy Receptor NDP52 in Microbial Infections

2020 ◽  
Vol 21 (6) ◽  
pp. 2008 ◽  
Author(s):  
Shuangqi Fan ◽  
Keke Wu ◽  
Mengpo Zhao ◽  
Erpeng Zhu ◽  
Shengming Ma ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Protective Mechanism ◽  
Pathogenic Microorganism ◽  
Microbial Infection ◽  
Selective Autophagy ◽  
Microbial Infections ◽  
Ubiquitin Proteasome ◽  
Cellular Components

Autophagy is a general protective mechanism for maintaining homeostasis in eukaryotic cells, regulating cellular metabolism, and promoting cell survival by degrading and recycling cellular components under stress conditions. The degradation pathway that is mediated by autophagy receptors is called selective autophagy, also named as xenophagy. Autophagy receptor NDP52 acts as a ‘bridge’ between autophagy and the ubiquitin-proteasome system, and it also plays an important role in the process of selective autophagy. Pathogenic microbial infections cause various diseases in both humans and animals, posing a great threat to public health. Increasing evidence has revealed that autophagy and autophagy receptors are involved in the life cycle of pathogenic microbial infections. The interaction between autophagy receptor and pathogenic microorganism not only affects the replication of these microorganisms in the host cell, but it also affects the host’s immune system. This review aims to discuss the effects of autophagy on pathogenic microbial infection and replication, and summarizes the mechanisms by which autophagy receptors interact with microorganisms. While considering the role of autophagy receptors in microbial infection, NDP52 might be a potential target for developing effective therapies to treat pathogenic microbial infections.

scholarly journals Atg8 Controls Phagophore Expansion during Autophagosome Formation

2008 ◽  
Vol 19 (8) ◽  
pp. 3290-3298 ◽  
Author(s):  
Zhiping Xie ◽  
Usha Nair ◽  
Daniel J. Klionsky
Keyword(s):  
Membrane Vesicles ◽  
Degradation Process ◽  
Autophagosome Formation ◽  
Multistage Model ◽  
Intracellular Degradation ◽  
Cytoplasmic Material ◽  
New Genes ◽  
Health And Disease ◽  
Time Observation ◽  
Related Proteins

Autophagy is a potent intracellular degradation process with pivotal roles in health and disease. Atg8, a lipid-conjugated ubiquitin-like protein, is required for the formation of autophagosomes, double-membrane vesicles responsible for the delivery of cytoplasmic material to lysosomes. How and when Atg8 functions in this process, however, is not clear. Here we show that Atg8 controls the expansion of the autophagosome precursor, the phagophore, and give the first real-time, observation-based temporal dissection of the autophagosome formation process. We demonstrate that the amount of Atg8 determines the size of autophagosomes. During autophagosome biogenesis, Atg8 forms an expanding structure and later dissociates from the site of vesicle formation. On the basis of the dynamics of Atg8, we present a multistage model of autophagosome formation. This model provides a foundation for future analyses of the functions and dynamics of known autophagy-related proteins and for screening new genes.

scholarly journals ATG8-Interacting Motif: Evolution and Function in Selective Autophagy of Targeting Biological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Wanqing Liu ◽  
Zinan Liu ◽  
Zulong Mo ◽  
Shaoying Guo ◽  
Yunfeng Liu ◽  
...  
Keyword(s):  
Dual Role ◽  
Current Understanding ◽  
Biological Processes ◽  
Docking Site ◽  
Selective Autophagy ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Cellular Components

Autophagy is an evolutionarily conserved vacuolar process functioning in the degradation of cellular components for reuse. In plants, autophagy is generally activated upon stress and its regulation is executed by numbers of AuTophaGy-related genes (ATGs), of which the ATG8 plays a dual role in both biogenesis of autophagosomes and recruitment of ATG8-interacting motif (AIM) anchored selective autophagy receptors (SARs). Such motif is either termed as AIM or ubiquitin-interacting motif (UIM), corresponding to the LC3-interacting region (LIR)/AIM docking site (LDS) or the UIM docking site (UDS) of ATG8, respectively. To date, dozens of AIM or UIM containing SARs have been characterized. However, the knowledge of these motifs is still obscured. In this review, we intend to summarize the current understanding of SAR proteins and discuss the conservation and diversification of the AIMs/UIMs, expectantly providing new insights into the evolution of them in various biological processes in plants.

scholarly journals Structural catalog of core Atg proteins opens new era of autophagy research

2021 ◽  
Author(s):  
Kazuaki Matoba ◽  
Nobuo N Noda
Keyword(s):  
De Novo ◽  
Structural Information ◽  
Membrane Dynamics ◽  
Autophagosome Formation ◽  
New Era ◽  
Intracellular Degradation ◽  
Atg Proteins ◽  
Biological Studies ◽  
Evolutionarily Conserved ◽  
Biological Methods

Summary Autophagy, which is an evolutionarily conserved intracellular degradation system, involves de novo generation of autophagosomes that sequester and deliver diverse cytoplasmic materials to the lysosome for degradation. Autophagosome formation is mediated by approximately 20 core autophagy-related (Atg) proteins, which collaborate to mediate complicated membrane dynamics during autophagy. To elucidate the molecular functions of these Atg proteins in autophagosome formation, many researchers have tried to determine the structures of Atg proteins by using various structural biological methods. Although not sufficient, the basic structural catalog of all core Atg proteins was established. In this review article, we summarize structural biological studies of core Atg proteins, with an emphasis on recently unveiled structures, and describe the mechanistic breakthroughs in autophagy research that have derived from new structural information.

Phylogeny accurately predicts behaviour in Indian Ocean Clitaetra spiders (Araneae:Nephilidae)

2009 ◽  
Vol 23 (3) ◽  
pp. 193 ◽  
Author(s):  
Matjaž Kuntner ◽  
Ingi Agnarsson
Keyword(s):  
South Africa ◽  
Phylogenetic Analysis ◽  
Indian Ocean ◽  
Species Level ◽  
Web Architecture ◽  
Evolutionarily Conserved ◽  
The Family ◽  
Behavioural Biology

Phylogenies are underutilised, powerful predictors of traits in unstudied species. We tested phylogenetic predictions of web-related behaviour in Clitaetra Simon, 1889, an Afro-Indian spider genus of the family Nephilidae. Clitaetra is phylogenetically sister to all other nephilids and thus important for understanding ancestral traits. Behavioural information on Clitaetra has been limited to only C. irenae Kuntner, 2006 from South Africa which constructs ladder webs. A resolved species-level phylogeny unambiguously optimised Clitaetra behavioural biology and predicted web traits in five unstudied species and a uniform intrageneric nephilid web biology. We tested these predictions by studying the ecology and web biology of C. perroti Simon, 1894 on Madagascar and C. episinoides Simon, 1889 on Mayotte. We confirm predicted arboricolous web architecture in these species. The expected ontogenetic allometric transition from orbs in juveniles to elongate ladder webs in adults was statistically significant in C. perroti, whereas marginally not significant in C. episinoides. We demonstrate the persistence of the temporary spiral in finished Clitaetra webs. A morphological and behavioural phylogenetic analysis resulted in unchanged topology and persisting unambiguous behavioural synapomorphies. Our results support the homology of Clitaetra hub reinforcement with the nephilid hub-cup. In Clitaetra, behaviour was highly predictable and remained consistent with new observations. Our results confirm that nephilid web biology is evolutionarily conserved within genera.

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