PXD013719

PXD013719 is an original dataset announced via ProteomeXchange.

Title	RAB18 impacts autophagy via lipid droplet-derived lipid transfer and is rescued by ATG9A
Description	Autophagy is a lysosomal degradation pathway that mediates protein and organelle turnover and maintains cellular homeostasis. Autophagosomes transport cargo to lysosomes and their formation is dependent on an appropriate lipid supply. Here, we show that the knockout of the RAB GTPase RAB18 interferes with lipid droplet (LD) metabolism, resulting in an impaired fatty acid mobilization. The reduced LD-derived lipid availability influences autophagy and provokes adaptive modifications of the autophagy network, which include increased ATG2B expression and ATG12-ATG5 conjugate formation as well as enhanced ATG2B and ATG9A phosphorylation. Phosphorylation of ATG9A directs this transmembrane protein to the site of autophagosome formation and this particular modification is sufficient to rescue autophagic activity under basal conditions in the absence of RAB18. However, it is incapable of enabling an increased autophagy under inductive conditions. Thus, we illustrate the role of RAB18 in connecting LDs and autophagy, further emphasize the importance of LD-derived lipids for the degradative pathway, and characterize an ATG9A phosphorylation-dependent autophagy rescue mechanism as an adaptive response that maintains autophagy under conditions of reduced LD-derived lipid availability.
HostingRepository	PRIDE
AnnounceDate	2020-01-29
AnnouncementXML	Submission_2020-01-29_04:30:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-06 07:25:14	ID requested
⏵ 1	2020-01-29 04:30:03	announced

Bekbulat F, Schmitt D, Feldmann A, Huesmann H, Eimer S, Juretschke T, Beli P, Behl C, Kern A, RAB18 Loss Interferes With Lipid Droplet Catabolism and Provokes Autophagy Network Adaptations. J Mol Biol, 432(4):1216-1234(2020) [pubmed]

curator keyword: Biological

submitter keyword: Human, LC-MS/MS, Rab18, ATG2B, ATG9A

Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD013719

PRIDE project URI

• PRIDE
  1. PXD013719
     1. Label: PRIDE project
     2. Name: RAB18 impacts autophagy via lipid droplet-derived lipid transfer and is rescued by ATG9A