PXD052945

PXD052945 is an original dataset announced via ProteomeXchange.

Title	The V-ATPase/ATG16L1 axis is controlled by the V1H subunit
Description	Defects in organellar acidification indicate compromised or infected compartments. Recruitment of the autophagy-related ATG16L1 complex to pathologically de-acidified compartments targets ubiquitin-like ATG8 molecules to perturbed membranes. How this process is coupled to pH gradient disruption is unclear. Here, we reveal a direct role for the V1H subunit of the V-ATPase proton pump in recruiting ATG16L1. The interaction between V1H and ATG16L1 occurs within assembled V-ATPases, but not dissociated V1 complexes. This selectivity allows recruitment to be coupled to changes in V-ATPase assembly that follow pH dissipation. Cells lacking V1H undergo canonical macroautophagy but are unable to recruit ATG16L1 in response to influenza infection, STING activation or ionophore drugs. We identify a loop within V1H that mediates ATG16L1 binding, which is absent in a neuronal isoform of V1H. Thus, V1H controls ATG16L1 recruitment in response to proton gradient dissipation, suggesting that the V-ATPase acts autonomously as a cell-intrinsic damage sensor.
HostingRepository	PRIDE
AnnounceDate	2025-01-30
AnnouncementXML	Submission_2025-01-30_10:05:02.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Skehel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-08 23:08:59	ID requested
⏵ 1	2025-01-30 10:05:02	announced

10.1016/J.MOLCEL.2024.07.003;

submitter keyword: Human, lysosome, V-ATPase, pH gradient

Rupert Beale
contact affiliation	Cell Biology of Infection Laboratory, The Francis Crick Institute, London, UK Division of Medicine, University College London, London, UK
contact email	rupert.beale@crick.ac.uk
lab head
Mark Skehel
contact affiliation	Francis Crick Institute
contact email	skehelm@crick.ac.uk
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/2025/01/PXD052945

PRIDE project URI

• PRIDE
  1. PXD052945
     1. Label: PRIDE project
     2. Name: The V-ATPase/ATG16L1 axis is controlled by the V1H subunit