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Cell Research Jul 2020
Topics: Animals; Autophagosomes; Autophagy; Disease; Humans; Lysosomes
PubMed: 32572279
DOI: 10.1038/s41422-020-0361-2 -
Molecular Cell Oct 2019The clearance of surplus, broken, or dangerous components is key for maintaining cellular homeostasis. The failure to remove protein aggregates, damaged organelles, or... (Review)
Review
The clearance of surplus, broken, or dangerous components is key for maintaining cellular homeostasis. The failure to remove protein aggregates, damaged organelles, or intracellular pathogens leads to diseases, including neurodegeneration, cancer, and infectious diseases. Autophagy is the evolutionarily conserved pathway that sequesters cytoplasmic components in specialized vesicles, autophagosomes, which transport the cargo to the degradative compartments (vacuoles or lysosomes). Research during the past few decades has elucidated how autophagosomes engulf their substrates selectively. This type of autophagy involves a growing number of selective autophagy receptors (SARs) (e.g., Atg19 in yeasts, p62/SQSTM1 in mammals), which bind to the cargo and simultaneously engage components of the core autophagic machinery via direct interaction with the ubiquitin-like proteins (UBLs) of the Atg8/LC3/GABARAP family and adaptors, Atg11 (in yeasts) or FIP200 (in mammals). In this Review, we critically discuss the biology of the SARs with special emphasis on their interactions with UBLs.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Binding Sites; Fungal Proteins; Humans; Ligands; Protein Binding; Protein Interaction Domains and Motifs; Signal Transduction; Ubiquitination; Ubiquitins; Yeasts
PubMed: 31585693
DOI: 10.1016/j.molcel.2019.09.005 -
Autophagy Mar 2024Macroautophagy/autophagy receptors target their substrates to phagophores for subsequent sequestration within autophagosomes. During phagophore membrane expansion in...
Macroautophagy/autophagy receptors target their substrates to phagophores for subsequent sequestration within autophagosomes. During phagophore membrane expansion in mammalian cells, autophagy receptors simultaneously interact with the ubiquitinated substrates and the LC3/GABARAP proteins on the expanding membrane. In this punctum, we summarize and discuss our recent research progress on synthetic autophagy receptors (AceTACs). The series of AceTACs were designed by engineering the essential interacting domains and motifs of SQSTM1/p62 (sequestosome 1), a major mammalian autophagy receptor. Particularly, we replaced the ubiquitin-associated domain of SQSTM1 with a target-specific antibody, redirecting the bifunctional interactions of wild-type SQSTM1 and directing the degradation target into the autophagy process. We successfully demonstrated the targeted degradation of aggregation-prone proteins using the AceTAC degraders. Moreover, we presented a model system with a guideline to induce targeted degradation of organelles through the autophagy machinery.
Topics: Animals; Autophagy; Sequestosome-1 Protein; Proteins; Autophagosomes; Ubiquitin; Carrier Proteins; Mammals
PubMed: 37934826
DOI: 10.1080/15548627.2023.2278954 -
International Journal of Molecular... Jun 2023Exosomes, which are extracellular vesicles (EVs) predominantly present in bodily fluids, participate in various physiological processes. Autophagy, an intracellular... (Review)
Review
Exosomes, which are extracellular vesicles (EVs) predominantly present in bodily fluids, participate in various physiological processes. Autophagy, an intracellular degradation mechanism, eliminates proteins and damaged organelles by forming double-membrane autophagosomes. These autophagosomes subsequently merge with lysosomes for target degradation. The interaction between autophagy and endosomal/exosomal pathways can occur at different stages, exerting significant influences on normal physiology and human diseases. The interplay between exosomes and the autophagy pathway is intricate. Exosomes exhibit a cytoprotective role by inducing intracellular autophagy, while autophagy modulates the biogenesis and degradation of exosomes. Research indicates that exosomes and autophagy contribute to the infection process of numerous enveloped viruses. Enveloped viruses, comprising viral nucleic acid, proteins, or virions, can be encapsulated within exosomes and transferred between cells via exosomal transport. Consequently, exosomes play a crucial role in the infection of certain viral diseases. This review presents recent findings on the interplay between exosomes and autophagy, as well as their implications in the infection of enveloped viruses, thereby offering valuable insights into the pathogenesis and vaccine research of enveloped virus infection.
Topics: Humans; Exosomes; Autophagy; Endosomes; Extracellular Vesicles; Autophagosomes
PubMed: 37445802
DOI: 10.3390/ijms241310618 -
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 -
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 -
Nature Structural & Molecular Biology Nov 2022
Topics: Autophagosomes; Calcium; Microtubule-Associated Proteins; Autophagy; Lysosomes
PubMed: 36352140
DOI: 10.1038/s41594-022-00869-6 -
Autophagy Dec 2023Over the past decade, accumulated studies have reported the presence of non-canonical macroautophagy/autophagy characterized by the shared usage of the autophagy...
Over the past decade, accumulated studies have reported the presence of non-canonical macroautophagy/autophagy characterized by the shared usage of the autophagy machinery and distinct components that function in multiple scenarios but do not involve lysosomal degradation. One type of non-canonical autophagy is secretory autophagy, which facilitates the secretion of various cargoes. In a recent work from Gao et al. the ER-membrane protein STING1 has been identified as a novel substrate of secretory autophagy. The secretion of activated STING1 is mediated by its packing into the rafeesome, a newly identified organelle formed upon the fusion of RAB22A-mediated non-canonical autophagosome with an early endosome. Moreover, extracellular vesicles containing activated STING1 induce antitumor immunity in recipient cells, a process potentially promoted by RAB22A.
Topics: Autophagy; Autophagosomes; Lysosomes; Membrane Proteins; Endoplasmic Reticulum
PubMed: 37543953
DOI: 10.1080/15548627.2023.2240154 -
Cells Apr 2023Autophagy is a highly conserved recycling process of eukaryotic cells that degrades protein aggregates or damaged organelles with the participation of autophagy-related... (Review)
Review
Autophagy is a highly conserved recycling process of eukaryotic cells that degrades protein aggregates or damaged organelles with the participation of autophagy-related proteins. Membrane bending is a key step in autophagosome membrane formation and nucleation. A variety of autophagy-related proteins (ATGs) are needed to sense and generate membrane curvature, which then complete the membrane remodeling process. The Atg1 complex, Atg2-Atg18 complex, Vps34 complex, Atg12-Atg5 conjugation system, Atg8-phosphatidylethanolamine conjugation system, and transmembrane protein Atg9 promote the production of autophagosomal membranes directly or indirectly through their specific structures to alter membrane curvature. There are three common mechanisms to explain the change in membrane curvature. For example, the BAR domain of Bif-1 senses and tethers Atg9 vesicles to change the membrane curvature of the isolation membrane (IM), and the Atg9 vesicles are reported as a source of the IM in the autophagy process. The amphiphilic helix of Bif-1 inserts directly into the phospholipid bilayer, causing membrane asymmetry, and thus changing the membrane curvature of the IM. Atg2 forms a pathway for lipid transport from the endoplasmic reticulum to the IM, and this pathway also contributes to the formation of the IM. In this review, we introduce the phenomena and causes of membrane curvature changes in the process of macroautophagy, and the mechanisms of ATGs in membrane curvature and autophagosome membrane formation.
Topics: Autophagy; Cell Membrane; Proteolysis; Protein Aggregates; Autophagosomes; Autophagy-Related Proteins; Protein Domains; Lipid Bilayers; Humans
PubMed: 37190041
DOI: 10.3390/cells12081132 -
FEBS Letters Jan 2024Autophagy is an intracellular catabolic process that eliminates cytoplasmic constituents selectively by tight engulfment in an isolation membrane or recycles bulk... (Review)
Review
Autophagy is an intracellular catabolic process that eliminates cytoplasmic constituents selectively by tight engulfment in an isolation membrane or recycles bulk cytoplasm by nonselective sequestration. Completion of the isolation membrane forms a double membrane vesicle, termed autophagosome, that proceeds to fusion with the lysosome, where the inner membrane and its cytoplasmic content are degraded. Autophagosome biogenesis is unique in that the newly-formed membrane, termed phagophore, is elongated by direct lipid flow from a proximal ER-associated donor membrane. Recent years mark a tremendous advancement in delineating the direct regulation of this process by different lipid species and associated protein complexes. Here we schematically summarize the current view of autophagy and autophagosome biogenesis.
Topics: Autophagy; Autophagosomes; Lysosomes; Lipids
PubMed: 37326419
DOI: 10.1002/1873-3468.14679