An ESCRT-dependent step in fatty acid transfer from lipid droplets to mitochondria through VPS13D−TSG101 interactions DOI Creative Commons
Jingru Wang, Na Fang, Juan Xiong

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Feb. 23, 2021

Abstract Upon starvation, cells rewire their metabolism, switching from glucose-based metabolism to mitochondrial oxidation of fatty acids, which require the transfer FAs lipid droplets (LDs) mitochondria at mitochondria−LD membrane contact sites (MCSs). However, factors responsible for FA these MCSs remain uncharacterized. Here, we demonstrate that vacuolar protein sorting-associated 13D (VPS13D), loss-of-function mutations cause spastic ataxia, coordinates trafficking in conjunction with endosomal sorting complex required transport (ESCRT) tumor susceptibility 101 (TSG101). The VPS13 adaptor-binding domain VPS13D and TSG101 directly remodels LD membranes a cooperative manner. human binds glycerophospholipids vitro. Depletion VPS13D, TSG101, or ESCRT-III proteins inhibits LDs mitochondria. Our findings suggest mediates ESCRT-dependent remodeling facilitate mitochondria-LD contacts.

Language: Английский

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

Daniel J. Klionsky,

Amal Kamal Abdel‐Aziz, Sara Abdelfatah

et al.

Autophagy, Journal Year: 2021, Volume and Issue: 17(1), P. 1 - 382

Published: Jan. 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

Language: Английский

Citations

2004
Lysosomes as dynamic regulators of cell and organismal homeostasis DOI
Andrea Ballabio, Juan S. Bonifacino

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(2), P. 101 - 118

Published: Nov. 25, 2019

Language: Английский

Citations

1100
The lysosome as a cellular centre for signalling, metabolism and quality control DOI
Rosalie Lawrence, Roberto Zoncu

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(2), P. 133 - 142

Published: Dec. 20, 2018

Language: Английский

Citations

787
The functional universe of membrane contact sites DOI
William A. Prinz,

Alexandre Toulmay,

Tamás Balla

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 21(1), P. 7 - 24

Published: Nov. 15, 2019

Language: Английский

Citations

562
ATG2 transports lipids to promote autophagosome biogenesis DOI Creative Commons
Diana P. Valverde, Shenliang Yu, Rajendra Boggavarapu

et al.

The Journal of Cell Biology, Journal Year: 2019, Volume and Issue: 218(6), P. 1787 - 1798

Published: April 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.

Language: Английский

Citations

464
Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes DOI
Louise H. Wong, Alberto T. Gatta, Tim P. Levine

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2018, Volume and Issue: 20(2), P. 85 - 101

Published: Oct. 18, 2018

Language: Английский

Citations

424
Atg2 mediates direct lipid transfer between membranes for autophagosome formation DOI

Takuo Osawa,

Tetsuya Kotani,

Tatsuya Kawaoka

et al.

Nature Structural & Molecular Biology, Journal Year: 2019, Volume and Issue: 26(4), P. 281 - 288

Published: March 25, 2019

Language: Английский

Citations

400
The autophagic membrane tether ATG2A transfers lipids between membranes DOI Creative Commons
Shintaro Maeda,

Chinatsu Otomo,

Takanori Otomo

et al.

eLife, Journal Year: 2019, Volume and Issue: 8

Published: July 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.

Language: Английский

Citations

289
Autophagosome biogenesis: From membrane growth to closure DOI Creative Commons
Thomas J. Melia, Alf Håkon Lystad, Anne Simonsen

et al.

The Journal of Cell Biology, Journal Year: 2020, Volume and Issue: 219(6)

Published: May 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.

Language: Английский

Citations

270
Autophagy in Neurons DOI
Andrea KH Stavoe, Erika L.F. Holzbaur

Annual Review of Cell and Developmental Biology, Journal Year: 2019, Volume and Issue: 35(1), P. 477 - 500

Published: July 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.

Language: Английский

Citations

268