V-ATPase is a universal regulator of LC3-associated phagocytosis and non-canonical autophagy

Hooper, Kirsty M.; Jacquin, Élise; Li, Taoyingnan; Goodwin, Jonathan M.; Brumell, John H.; Durgan, Joanne; Florey, Oliver

doi:10.1083/jcb.202105112

Cited by 64 publications

(71 citation statements)

References 63 publications

(114 reference statements)

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“…LAP does not require the ULK complex but does require the ATG conjugation systems. Notably, the WD40 repeat domain of ATG16L1, which is absent in yeast Atg16 (Table 1 ), is essential for LAP through binding to V-ATPase, but not for canonical autophagy 72 – 76 . The PI3KC3–C2 component UVRAG and RUBCN are also required.…”

Section: Genes Regulating Macroautophagymentioning

confidence: 99%

Autophagy genes in biology and disease

2023

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Macroautophagy and microautophagy are highly conserved eukaryotic cellular processes that degrade cytoplasmic material in lysosomes. Both pathways involve characteristic membrane dynamics regulated by autophagy-related proteins and other molecules, some of which are shared between the two pathways. Over the past few years, the application of new technologies, such as cryo-electron microscopy, coevolution-based structural prediction and in vitro reconstitution, has revealed the functions of individual autophagy gene products, especially in autophagy induction, membrane reorganization and cargo recognition. Concomitantly, mutations in autophagy genes have been linked to human disorders, particularly neurodegenerative diseases, emphasizing the potential pathogenic implications of autophagy defects. Accumulating genome data have also illuminated the evolution of autophagy genes within eukaryotes as well as their transition from possible ancestral elements in prokaryotes.

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Section: Genes Regulating Macroautophagymentioning

confidence: 99%

Autophagy genes in biology and disease

2023

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“…Depending on the membrane type, this can have alternative outcomes spanning from degradation to secretion or membrane repair ( Kakanj et al, 2022 ; Vats and Galli, 2022 ). The process, which has also been referred to as conjugation of ATG8 to single membranes (CASM) is summarized in Figure 2 , can both involve classical ATG8 conjugation to PE, or alternatively to PS, as described above ( Durgan et al, 2021 ; Hooper et al, 2022 ). Interestingly, single membrane lipidation has limited dependency on the classical upstream autophagy initiation machinery including mTOR and ULK1 complexes, while still engaging most of the canonical ubiquitin-like conjugation program.…”

Section: Recruitment Of Atg8 To Single Membranesmentioning

confidence: 99%

Canonical and non-canonical roles for ATG8 proteins in autophagy and beyond

Reid

Kolapalli

Nielsen

et al. 2022

Front. Mol. Biosci.

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During autophagy, the ATG8 family proteins have several well-characterized roles in facilitating early, mid, and late steps of autophagy, including autophagosome expansion, cargo recruitment and autophagosome-lysosome fusion. Their discovery has importantly allowed for precise experimental monitoring of the pathway, bringing about a huge expansion of research in the field over the last decades. In this review, we discuss both canonical and non-canonical roles of the autophagic lipidation machinery, with particular focus on the ATG8 proteins, their post-translational modifications and their increasingly uncovered alternative roles mediated through their anchoring at different membranes. These include endosomes, macropinosomes, phagosomes and the plasma membrane, to which ATG8 proteins can bind through canonical or alternative lipidation. Beyond new ATG8 binding partners and cargo types, we also explore several open questions related to alternative outcomes of autophagic machinery engagement beyond degradation. These include their roles in plasma membrane repair and secretion of selected substrates as well as the physiological implications hereof in health and disease.

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“…In addition to its relatively well-characterized role in the Cvt pathway and secretory autophagy, the autophagy machinery (or autophagy genes) has been implicated in many other cellular events, ranging from DNA repair to cell division to T-cell differentiation. A recent review provides a more comprehensive description of the non-canonical functions of the autophagy machinery [ 53 ], which are becoming a new research hotspot [ 54 , 55 , 56 ].…”

Section: Pro-survival Roles Of the Autophagy Machinery Independent Of...mentioning

confidence: 99%

Life and Death Decisions—The Many Faces of Autophagy in Cell Survival and Cell Death

Klionsky

2022

Biomolecules

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Autophagy is a process conserved from yeast to humans. Since the discovery of autophagy, its physiological role in cell survival and cell death has been intensively investigated. The inherent ability of the autophagy machinery to sequester, deliver, and degrade cytoplasmic components enables autophagy to participate in cell survival and cell death in multiple ways. The primary role of autophagy is to send cytoplasmic components to the vacuole or lysosomes for degradation. By fine-tuning autophagy, the cell regulates the removal and recycling of cytoplasmic components in response to various stress or signals. Recent research has shown the implications of the autophagy machinery in other pathways independent of lysosomal degradation, expanding the pro-survival role of autophagy. Autophagy also facilitates certain forms of regulated cell death. In addition, there is complex crosstalk between autophagy and regulated cell death pathways, with a number of genes shared between them, further suggesting a deeper connection between autophagy and cell death. Finally, the mitochondrion presents an example where the cell utilizes autophagy to strike a balance between cell survival and cell death. In this review, we consider the current knowledge on the physiological role of autophagy as well as its regulation and discuss the multiple functions of autophagy in cell survival and cell death.

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V-ATPase is a universal regulator of LC3-associated phagocytosis and non-canonical autophagy

Cited by 64 publications

References 63 publications

Autophagy genes in biology and disease

Autophagy genes in biology and disease

Canonical and non-canonical roles for ATG8 proteins in autophagy and beyond

Life and Death Decisions—The Many Faces of Autophagy in Cell Survival and Cell Death

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