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Cell Research Jul 2020
Topics: Animals; Autophagosomes; Autophagy; Disease; Humans; Lysosomes
PubMed: 32572279
DOI: 10.1038/s41422-020-0361-2 -
Journal of Experimental Botany May 2020Autophagy is a universal mechanism that facilitates the degradation of unwanted cytoplasmic components in eukaryotic cells. In this review, we highlight recent... (Review)
Review
Autophagy is a universal mechanism that facilitates the degradation of unwanted cytoplasmic components in eukaryotic cells. In this review, we highlight recent developments in the investigation of the role of autophagy in lipid homeostasis in plants by comparison with algae, yeast, and animals. We consider the storage compartments that form the sources of lipids in plants, and the roles that autophagy plays in the synthesis of triacylglycerols and in the formation and maintenance of lipid droplets. We also consider the relationship between lipids and the biogenesis of autophagosomes, and the role of autophagy in the degradation of lipids in plants.
Topics: Animals; Autophagosomes; Autophagy; Lipid Droplets; Lipids; Plants
PubMed: 32080724
DOI: 10.1093/jxb/eraa082 -
Autophagy Nov 2021It would be quite convenient if every protein had one distinct function, one distinct role in just a single cellular process. In the field of macroautophagy/autophagy,...
It would be quite convenient if every protein had one distinct function, one distinct role in just a single cellular process. In the field of macroautophagy/autophagy, however, we are increasingly finding that this is not the case; several autophagy proteins have two or more roles within the process of autophagy and many even "moonlight" as functional members of entirely different cellular processes. This is perhaps best exemplified by the Atg8-family proteins. These dynamic proteins have already been reported to serve several functions both within autophagy (membrane tethering, membrane fusion, binding to cargo receptors, binding to autophagy machinery) and beyond (LC3-associated phagocytosis, formation of EDEMosomes, immune signaling) but as Maruyama and colleagues suggest in their recent report, this list of functions may not yet be complete.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Protein 8 Family; Binding Sites; Humans; Models, Molecular; Molecular Docking Simulation; Mutation
PubMed: 34482799
DOI: 10.1080/15548627.2021.1967566 -
Molecular Cell Mar 2021Autophagy deficiency in fed conditions leads to the formation of protein inclusions highlighting the contribution of this lysosomal delivery route to cellular...
Autophagy deficiency in fed conditions leads to the formation of protein inclusions highlighting the contribution of this lysosomal delivery route to cellular proteostasis. Selective autophagy pathways exist that clear accumulated and aggregated ubiquitinated proteins. Receptors for this type of autophagy (aggrephagy) include p62, NBR1, TOLLIP, and OPTN, which possess LC3-interacting regions and ubiquitin-binding domains (UBDs), thus working as a bridge between LC3/GABARAP proteins and ubiquitinated substrates. However, the identity of aggrephagy substrates and the redundancy of aggrephagy and related UBD-containing receptors remains elusive. Here, we combined proximity labeling and organelle enrichment with quantitative proteomics to systematically map the autophagic degradome targeted by UBD-containing receptors under basal and proteostasis-challenging conditions in human cell lines. We identified various autophagy substrates, some of which were differentially engulfed by autophagosomal and endosomal membranes via p62 and TOLLIP, respectively. Overall, this resource will allow dissection of the proteostasis contribution of autophagy to numerous individual proteins.
Topics: Autophagosomes; Autophagy; Autophagy-Related Proteins; HEK293 Cells; HeLa Cells; Humans; Protein Interaction Maps; Proteolysis; Proteomics; Proteostasis; Ubiquitination
PubMed: 33545068
DOI: 10.1016/j.molcel.2021.01.009 -
Protein & Cell Jul 2021Autophagy is essential for the maintenance of cellular homeostasis and its dysfunction has been linked to various diseases. Autophagy is a membrane driven process and... (Review)
Review
Autophagy is essential for the maintenance of cellular homeostasis and its dysfunction has been linked to various diseases. Autophagy is a membrane driven process and tightly regulated by membrane-associated proteins. Here, we summarized membrane lipid composition, and membrane-associated proteins relevant to autophagy from a spatiotemporal perspective. In particular, we focused on three important membrane remodeling processes in autophagy, lipid transfer for phagophore elongation, membrane scission for phagophore closure, and autophagosome-lysosome membrane fusion. We discussed the significance of the discoveries in this field and possible avenues to follow for future studies. Finally, we summarized the membrane-associated biochemical techniques and assays used to study membrane properties, with a discussion of their applications in autophagy.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Biological Transport; Cell Membrane; Endosomal Sorting Complexes Required for Transport; Gene Expression; Homeostasis; Intracellular Membranes; Lysosomes; Mammals; Membrane Fusion; Membrane Lipids; Membrane Proteins; Saccharomyces cerevisiae; Vesicular Transport Proteins
PubMed: 33151516
DOI: 10.1007/s13238-020-00793-9 -
Journal of Neurochemistry Aug 2021Neurons, because of their elaborate morphology and the long distances between distal axons and the soma as well as their longevity, pose special challenges to autophagy... (Review)
Review
Neurons, because of their elaborate morphology and the long distances between distal axons and the soma as well as their longevity, pose special challenges to autophagy and to the endolysosomal system, two of the main degradative routes for turnover of defective proteins and organelles. Autophagosomes sequester cytoplasmic or organellar cargos by engulfing them into their lumen before fusion with degradative lysosomes enriched in neuronal somata and participate in retrograde signaling to the soma. Endosomes are mainly involved in the sorting, recycling, or lysosomal turnover of internalized or membrane-bound macromolecules to maintain axonal membrane homeostasis. Lysosomes and the multiple shades of lysosome-related organelles also serve non-degradative roles, for example, in nutrient signaling and in synapse formation. Recent years have begun to shed light on the distinctive organization of the autophagy and endolysosomal systems in neurons, in particular their roles in axons. We review here our current understanding of the localization, distribution, and growing list of functions of these organelles in the axon in health and disease and outline perspectives for future research.
Topics: Animals; Autophagosomes; Autophagy; Axons; Endosomes; Humans; Lysosomes; Membrane Transport Proteins; Neurons; Protein Transport
PubMed: 33372296
DOI: 10.1111/jnc.15287 -
Developmental Cell Dec 2023The sequence of morphological intermediates that leads to mammalian autophagosome formation and closure is a crucial yet poorly understood issue. Previous studies have...
The sequence of morphological intermediates that leads to mammalian autophagosome formation and closure is a crucial yet poorly understood issue. Previous studies have shown that yeast autophagosomes evolve from cup-shaped phagophores with only one closure point, and mammalian studies have inferred that mammalian phagophores also have single openings. Our superresolution microscopy studies in different human cell lines in conditions of basal and nutrient-deprivation-induced autophagy identified autophagosome precursors with multifocal origins that evolved into unexpected finger-like phagophores with multiple openings before becoming more spherical structures. Compatible phagophore structures were observed with whole-mount and conventional electron microscopy. This sequence of events was visualized using advanced SIM superresolution live microscopy. The finger-shaped phagophore apertures remained open when ESCRT function was compromised. The efficient closure of autophagic structures is important for their release from the recycling endosome. This has important implications for understanding how autophagosomes form and capture various cargoes.
Topics: Animals; Humans; Autophagosomes; Autophagy; Endosomes; Cell Line; Phagocytosis; Mammals
PubMed: 37683632
DOI: 10.1016/j.devcel.2023.08.016 -
Cells Oct 2021Autophagy and the lysosomal system, together referred to as the autophagolysosomal system, is a cellular quality control network which maintains cellular health and... (Review)
Review
Autophagy and the lysosomal system, together referred to as the autophagolysosomal system, is a cellular quality control network which maintains cellular health and homeostasis by removing cellular waste including protein aggregates, damaged organelles, and invading pathogens. As such, the autophagolysosomal system has roles in a variety of pathophysiological disorders, including cancer, neurological disorders, immune- and inflammation-related diseases, and metabolic alterations, among others. The autophagolysosomal system is controlled by TFEB, a master transcriptional regulator driving the expression of multiple genes, including autophagoly sosomal components. Importantly, Reactive Oxygen Species (ROS) production and control are key aspects of the physiopathological roles of the autophagolysosomal system, and may hold a key for synergistic therapeutic interventions. In this study, we reviewed our current knowledge on the biology and physiopathology of the autophagolysosomal system, and its potential for therapeutic intervention in cancer.
Topics: Animals; Autophagosomes; Autophagy; Homeostasis; Humans; Lysosomes; Nanomedicine; Neoplasms
PubMed: 34685734
DOI: 10.3390/cells10102752 -
Journal of Molecular Biology Feb 2017Macroautophagy, or simply autophagy, is a degradative pathway that delivers cytoplasmic components, including cytosol and organelles, to the lysosome in double-membrane... (Review)
Review
Macroautophagy, or simply autophagy, is a degradative pathway that delivers cytoplasmic components, including cytosol and organelles, to the lysosome in double-membrane vesicles called autophagosomes. This process is initiated at the pre-autophagosomal structure or phagophore assembly site and involves a number of highly conserved autophagy-related proteins. These support the generation and conversion of an open membranous cistern known as the phagophore or isolation membrane into a closed autophagosome. Within this review, we will focus on recent insights into the molecular events following the sealing/completion of an autophagosome, which lead to its maturation and subsequent fusion with endosomes/lysosomes.
Topics: Animals; Autophagosomes; Autophagy; Cytosol; Endosomes; Humans; Lysosomes; Mammals; SNARE Proteins; Yeasts
PubMed: 28077293
DOI: 10.1016/j.jmb.2017.01.002 -
Biochemical Society Transactions Feb 2022Macroautophagy, hereafter autophagy, is a degradative process conserved among eukaryotes, which is essential to maintain cellular homeostasis. Defects in autophagy lead... (Review)
Review
Macroautophagy, hereafter autophagy, is a degradative process conserved among eukaryotes, which is essential to maintain cellular homeostasis. Defects in autophagy lead to numerous human diseases, including various types of cancer and neurodegenerative disorders. The hallmark of autophagy is the de novo formation of autophagosomes, which are double-membrane vesicles that sequester and deliver cytoplasmic materials to lysosomes/vacuoles for degradation. The mechanism of autophagosome biogenesis entered a molecular era with the identification of autophagy-related (ATG) proteins. Although there are many unanswered questions and aspects that have raised some controversies, enormous advances have been done in our understanding of the process of autophagy in recent years. In this review, we describe the current knowledge about the molecular regulation of autophagosome formation, with a particular focus on budding yeast and mammalian cells.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Humans; Lysosomes; Macroautophagy; Mammals
PubMed: 35076688
DOI: 10.1042/BST20210819