A possible role for VPS13-family proteins in bulk lipid transfer, membrane expansion and organelle biogenesis DOI Creative Commons
Thomas J. Melia, Karin M. Reinisch

Journal of Cell Science, Journal Year: 2022, Volume and Issue: 135(5)

Published: March 1, 2022

At organelle-organelle contact sites, proteins have long been known to facilitate the rapid movement of lipids. Classically, this lipid transport involves extraction single lipids into a hydrophobic pocket on protein. Recently, new class transporter has described with physical characteristics that suggest these are likely function differently. They possess tracts can bind many at once and physically span entire gulf between membranes suggesting they may act as bridges bulk flow. Here, we review what learned regarding structure transporters, whose best characterized members VPS13 ATG2 proteins, their apparent coordination other lipid-mobilizing organelle membranes. We also discuss prevailing hypothesis in field, type membrane expansion through delivery lipids, well emerging hypotheses questions surrounding novel proteins.

Language: Английский

Autophagy genes in biology and disease DOI Open Access
Hayashi Yamamoto, Sidi Zhang, Noboru Mizushima

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(6), P. 382 - 400

Published: Jan. 12, 2023

Language: Английский

Citations

365
TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis DOI Creative Commons
Dong Huang,

Bolin Xu,

Lu Liu

et al.

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(8), P. 1655 - 1670.e8

Published: May 19, 2021

Language: Английский

Citations

118
Macroautophagy in CNS health and disease DOI
Christopher J. Griffey, Ai Yamamoto

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(7), P. 411 - 427

Published: May 3, 2022

Language: Английский

Citations

93
ATG9A and ATG2A form a heteromeric complex essential for autophagosome formation DOI Creative Commons
Alexander R. van Vliet, George N. Chiduza, Sarah Maslen

et al.

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(22), P. 4324 - 4339.e8

Published: Nov. 1, 2022

ATG9A and ATG2A are essential core members of the autophagy machinery. is a lipid scramblase that allows equilibration lipids across membrane bilayer, whereas facilitates flow between tethered membranes. Although both have been functionally linked during formation autophagosomes, molecular details consequences their interaction remain unclear. By combining data from peptide arrays, crosslinking, hydrogen-deuterium exchange mass spectrometry together with cryoelectron microscopy, we propose model ATG9A-2A complex. Using this integrative structure modeling approach, identify several interfaces mediating would allow direct transfer into lipid-binding perpendicular branch ATG9A. Mutational analyses combined functional activity assays demonstrate importance for autophagy, thereby shedding light on protein complex at heart autophagy.

Language: Английский

Citations

91
Lipid droplets and cellular lipid flux DOI

Alyssa J. Mathiowetz,

James A. Olzmann

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(3), P. 331 - 345

Published: March 1, 2024

Language: Английский

Citations

80
A novel superfamily of bridge-like lipid transfer proteins DOI Creative Commons
Sarah D. Neuman, Tim P. Levine, Arash Bashirullah

et al.

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 32(11), P. 962 - 974

Published: April 28, 2022

Language: Английский

Citations

76
Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9 DOI Creative Commons
Sisi Yang, Daehun Park,

Laura Manning

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(5), P. 824 - 840.e10

Published: Jan. 21, 2022

Autophagy is a cellular degradation pathway essential for neuronal health and function. Autophagosome biogenesis occurs at synapses, locally regulated, increases in response to activity. The mechanisms that couple autophagosome synaptic activity remain unknown. In this study, we determine trafficking of ATG-9, the only transmembrane protein core autophagy pathway, links vesicle cycle with autophagy. ATG-9-positive vesicles C. elegans are generated from trans-Golgi network via AP-3-dependent budding delivered presynaptic sites. At sites, ATG-9 undergoes exo-endocytosis an activity-dependent manner. Mutations disrupt endocytosis, including lesion synaptojanin 1 associated Parkinson's disease, result abnormal accumulation clathrin-rich foci defects activity-induced Our findings uncover regulated key steps sites provide evidence couples cycle.

Language: Английский

Citations

73
ER as master regulator of membrane trafficking and organelle function DOI Creative Commons
Eva M. Wenzel, Liv Anker Elfmark, Harald Stenmark

et al.

The Journal of Cell Biology, Journal Year: 2022, Volume and Issue: 221(10)

Published: Aug. 23, 2022

The endoplasmic reticulum (ER), which occupies a large portion of the cytoplasm, is cell’s main site for biosynthesis lipids and carbohydrate conjugates, it essential folding, assembly, biosynthetic transport secreted proteins integral membrane proteins. discovery abundant contact sites (MCSs) between ER other compartments has revealed that, in addition to its secretory functions, plays key roles regulation organelle dynamics functions. In this review, we will discuss how regulates endosomes, lysosomes, autophagosomes, mitochondria, peroxisomes, Golgi apparatus via MCSs. Such occurs lipid Ca2+ transfer also control trans dephosphorylation reactions motility, positioning, fusion, fission. diverse controls organelles MCSs manifest as master regulator biology.

Language: Английский

Citations

70
ATG9 vesicles comprise the seed membrane of mammalian autophagosomes DOI Creative Commons
Taryn J. Olivas, Yumei Wu, Shenliang Yu

et al.

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(7)

Published: April 28, 2023

As the autophagosome forms, its membrane surface area expands rapidly, while volume is kept low. Protein-mediated transfer of lipids from another organelle to likely drives this expansion, but as these are only introduced into cytoplasmic-facing leaflet organelle, full growth also requires lipid scramblase activity. ATG9 harbors activity and essential formation; however, whether integrated mammalian autophagosomes remains unclear. Here we show that in absence transport, vesicles already competent collect proteins found on mature autophagosomes, including LC3-II. Further, use styrene-maleic acid particles reveal nanoscale organization protein LC3-II membranes; each fully expanding autophagosomes. The ratios two at different stages maturation demonstrate not continuously integrated, rather present seed become diluted membrane.

Language: Английский

Citations

60
Unconventional initiation of PINK1/Parkin mitophagy by Optineurin DOI Creative Commons
Thanh Ngoc Nguyen, Justyna Sawa‐Makarska, Grace Khuu

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(10), P. 1693 - 1709.e9

Published: May 1, 2023

Cargo sequestration is a fundamental step of selective autophagy in which cells generate double-membrane structure termed an "autophagosome" on the surface cargoes. NDP52, TAX1BP1, and p62 bind FIP200, recruits ULK1/2 complex to initiate autophagosome formation How OPTN initiates during remains unknown despite its importance neurodegeneration. Here, we uncover unconventional path PINK1/Parkin mitophagy initiation by that does not begin with FIP200 binding or require kinases. Using gene-edited cell lines vitro reconstitutions, show utilizes kinase TBK1, binds directly class III phosphatidylinositol 3-kinase I mitophagy. During NDP52 initiation, TBK1 functionally redundant ULK1/2, classifying TBK1's role as autophagy-initiating kinase. Overall, this work reveals mechanistically distinct highlights mechanistic plasticity pathways.

Language: Английский

Citations

54