PXD040191-2

PXD040191 is an original dataset announced via ProteomeXchange.

Title	A Lysosome membrane regeneration pathway depends on TBC1D15 and autophagic lysosomal reformation proteins
Description	Acute lysosomal membrane damage reduces the cellular population of functional lysosomes. However, these damaged lysosomes have a remarkable recovery potential independent of lysosomal biogenesis and remain unaffected in TFEB/TFE3-depleted cells. We combined proximity labelling based proteomics, biochemistry and high-resolution microscopy to unravel a new lysosomal membrane regeneration pathway which is dependent on ATG8, lysosomal membrane protein LIMP2, the Rab7 GAP TBC1D15, and proteins required for autophagic lysosomal reformation (ALR) including Dynamin2, Kinesin5B and Clathrin. Upon lysosomal damage, LIMP2 act as a lysophagy receptor to bind ATG8, which in turn recruits TBC1D15 to damaged membranes. TBC1D15 hydrolyses Rab7-GTP to segregate the damaged lysosomal mass and provides a scaffold to assemble and stabilize the ALR machinery, potentiating the formation of lysosomal tubulesand subsequent Dynamin2-dependent scission. TBC1D15-mediated lysosome regeneration was also observed in a cell culture model of oxalate nephropathy.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:36.777.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anshu Bhattacharya
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-16 14:02:55	ID requested
1	2023-03-07 05:30:56	announced
⏵ 2	2023-11-14 09:00:37	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: autophagy, lysosomal regeneration,lysosomes, autophagic lysosomal reformation, TBC family of proteins

Ivan Dikic
contact affiliation	Institute of Biochemistry II; University Hospital of Goethe University Frankfurt Building 75 ,Ground floor, Room 0.205 Theodor-Stern-Kai 7 60590 Frankfurt am Main, Germany
contact email	dikic@biochem2.uni-frankfurt.de
lab head
Anshu Bhattacharya
contact affiliation	Goethe University, Institute of Biochemistry 2, Buchmann Institute For Molecular Life Sciences
contact email	bhattacharya@med.uni-frankfurt.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/2023/03/PXD040191

PRIDE project URI

• PRIDE
  1. PXD040191
     1. Label: PRIDE project
     2. Name: A Lysosome membrane regeneration pathway depends on TBC1D15 and autophagic lysosomal reformation proteins