Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)¹

Autophagy, Год журнала: 2021, Номер 17(1), С. 1 - 382

Опубликована: Янв. 2, 2021

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered field. Our knowledge base relevant new technologies also been expanding. Thus, it is important to formulate on a regular basis updated monitoring autophagy different organisms. Despite numerous reviews, there continues be confusion regarding acceptable methods evaluate autophagy, especially multicellular eukaryotes. Here, present investigators select interpret examine related processes, reviewers provide realistic reasonable critiques reports that are focused these processes. These not meant dogmatic rules, because appropriateness any assay largely depends question being asked system used. Moreover, no individual perfect every situation, calling use multiple techniques properly monitor each experimental setting. Finally, several core components machinery implicated distinct autophagic processes (canonical noncanonical autophagy), implying genetic approaches block should rely targeting two or more autophagy-related genes ideally participate steps pathway. Along similar lines, proteins involved regulate other cellular pathways including apoptosis, all them can used as specific marker bona fide responses. critically discuss current assessing information they can, cannot, provide. ultimate goal encourage intellectual technical innovation

Язык: Английский

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Lysosomes as dynamic regulators of cell and organismal homeostasis

Nature Reviews Molecular Cell Biology, Год журнала: 2019, Номер 21(2), С. 101 - 118

Опубликована: Ноя. 25, 2019

Язык: Английский

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The lysosome as a cellular centre for signalling, metabolism and quality control

Nature Cell Biology, Год журнала: 2018, Номер 21(2), С. 133 - 142

Опубликована: Дек. 20, 2018

Язык: Английский

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The functional universe of membrane contact sites

Nature Reviews Molecular Cell Biology, Год журнала: 2019, Номер 21(1), С. 7 - 24

Опубликована: Ноя. 15, 2019

Язык: Английский

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ATG2 transports lipids to promote autophagosome biogenesis

The Journal of Cell Biology, Год журнала: 2019, Номер 218(6), С. 1787 - 1798

Опубликована: Апрель 5, 2019

During macroautophagic stress, autophagosomes can be produced continuously and in high numbers. Many different organelles have been reported as potential donor membranes for this sustained autophagosome growth, but specific machinery to support the delivery of lipid growing membrane has remained unknown. Here we show that autophagy protein, ATG2, without a clear function since its discovery over 20 yr ago, is fact lipid-transfer protein likely operating at ER-autophagosome interface. ATG2A bind tens glycerophospholipids once transfers lipids robustly vitro. An N-terminal fragment supports transfer vitro both necessary fully sufficient rescue blocked biogenesis ATG2A/ATG2B KO cells, implying regulation homeostasis major autophagy-dependent activity and, by extension, protein-mediated across contact sites principal contributor formation.

Язык: Английский

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Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes

Nature Reviews Molecular Cell Biology, Год журнала: 2018, Номер 20(2), С. 85 - 101

Опубликована: Окт. 18, 2018

Язык: Английский

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Atg2 mediates direct lipid transfer between membranes for autophagosome formation

Nature Structural & Molecular Biology, Год журнала: 2019, Номер 26(4), С. 281 - 288

Опубликована: Март 25, 2019

Язык: Английский

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The autophagic membrane tether ATG2A transfers lipids between membranes

eLife, Год журнала: 2019, Номер 8

Опубликована: Июль 4, 2019

An enigmatic step in de novo formation of the autophagosome membrane compartment is expansion precursor phagophore, which requires acquisition lipids to serve as building blocks. Autophagy-related 2 (ATG2), rod-shaped protein that tethers phosphatidylinositol 3-phosphate (PI3P)-enriched phagophores endoplasmic reticulum (ER), suggested be essential for phagophore expansion, but underlying mechanism remains unclear. Here, we demonstrate human ATG2A a lipid transfer protein. can extract from vesicles and unload them other vesicles. Lipid by more efficient between tethered than untethered The PI3P effectors WIPI4 WIPI1 associate stably PI3P-containing vesicles, thereby facilitating ATG2A-mediated tethering PI3P-free Based on these results, propose ATG2-mediated ER enables expansion.

Язык: Английский

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Autophagosome biogenesis: From membrane growth to closure

The Journal of Cell Biology, Год журнала: 2020, Номер 219(6)

Опубликована: Май 1, 2020

Autophagosome biogenesis involves de novo formation of a membrane that elongates to sequester cytoplasmic cargo and closes form double-membrane vesicle (an autophagosome). This process has remained enigmatic since its initial discovery >50 yr ago, but our understanding the mechanisms involved in autophagosome increased substantially during last 20 yr. Several key questions do remain open, however, including, What determines site nucleation? is origin lipid composition membrane? How sequestration regulated under nonselective selective types autophagy? review provides insight into core molecular underlying biogenesis, with specific emphasis on modeling events, highlights recent conceptual advances field.

Язык: Английский

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Autophagy in Neurons

Annual Review of Cell and Developmental Biology, Год журнала: 2019, Номер 35(1), С. 477 - 500

Опубликована: Июль 24, 2019

Autophagy is the major cellular pathway to degrade dysfunctional organelles and protein aggregates. particularly important in neurons, which are terminally differentiated cells that must last lifetime of organism. There both constitutive stress-induced pathways for autophagy catalyze turnover aged or damaged mitochondria, endoplasmic reticulum, other organelles, aggregated proteins. These required neurodevelopment as well maintenance neuronal homeostasis. Here we review core components autophagosome biogenesis, cell biology bulk selective neurons. Finally, discuss role development, homeostasis, aging links between deficits neurodegeneration.

Язык: Английский

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