Machinery, regulation and pathophysiological implications of autophagosome maturation

Abstract

Cells in multicellular organisms constantly experience diverse stresses, including protein misfolding, organelle damage, scarcity of nutrients/energy and invasion by pathogens. One mechanism exploited by cells to combat stresses is the lysosome-mediated degradation of intracellular components via autophagy. Autophagy involves the formation of an isolation membrane (or phagophore), which further expands and closes to form the double-membrane autophagosome 1-3 . The mechanism of autophagosome formation was excellently reviewed recently 3 . Various cellular materials can be sequestered in autophagosomes, including unselected cytosolic material or selected cargos such as protein aggregates, damaged organelles and pathogens. Following autophagosome closure via membrane abscission, cargos are delivered to the vacuole (yeasts and plants) or to lysosomes (animal cells) (for an overview of the autophagy process see [4][5][6][7][8] ; Box 1). After degradation of the autophagic cargo, the digested content in the autolysosomes is released and lysosomes are re-formed to sustain the autophagic flux (Box 2). A series of proteins encoded by ATG (autophagy-related) genes and EPG (ectopic PGL granules) genes -identified mainly from genetic screens in Saccharomyces cerevisiae and Caenorhabditis elegans, respectively -act at different membrane remodelling steps for autophagosome formation and maturation 3,4,9,10 .In yeast, autophagosomes are formed in the vicinity of and directly fuse with the much larger vacuole, whereas in multicellular organisms, newly formed autophagosomes fuse with different endolysosomal vesicles such as early/late endosomes and lysosomes to form non-degradative, single-membrane structures called 'amphisomes' , which gradually acquire

Notoginseng Triterpenes Inhibited Autophagy in Random Flaps via the Beclin-1/VPS34/LC3 Signaling Pathway to Improve Tissue Survival

“…Autophagy is referred to as the rough-surfaced endoplasmic reticulum of the ribosome area of doublemembrane package which is part of the cytoplasm and cell organelles. Protein compositions, such as the degradation of domestic demand autophagy, will form, and fusion with lysosomes forming autophagy-lysosome and degradation of the contents of the package to realize the metabolism of the cell itself and some cell organelles needs to be updated (Ariosa et al, 2021;Ganley, 2021;Zhao et al, 2021). In normal cells, small amounts of autophagy are maintained to retain cell homeostasis (Talukdar et al, 2021).…”

The Dual Role of Autophagy in Crizotinib-Treated ALK+ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise

“…Finally, to follow the current burst in cancer immunotherapies, it is of utmost importance to study the role of autophagy in ALK lymphoma cells immunogenicity, immune surveillance, and response to immunotherapies. Indeed, it is likely that, together with the ongoing development of autophagy-modulating drugs [22,[124][125][126], immune-checkpoint inhibitors [127,128], and ALK immunotherapies [107,108,129,130], this might lead in the near future to the better management of ALK + ALCL patients.…”

“…Finally, the autophagic cargo is degraded by the lysosomal enzymes and recycled into the cytoplasm. More details on this core autophagy machinery and its regulation can be found in other excellent dedicated reviews [20][21][22][23].…”

Cell Death and Survival Pathways Involving ATM Protein Kinase

“…Autophagy is a cellular degradation system that contributes to cell survival by recycling biomaterials under nutrient starved conditions [79,80]. Autophagy also contributes to cellular homeostasis by eliminating damaged proteins, which are harmful when they accumulate in cells.…”