PXD028852-1

PXD028852 is an original dataset announced via ProteomeXchange.

Title	Proteins enriched on damaged lysosomes in 293T
Description	Lysosomal membrane permeabilization (LMP) or lysosomal membrane damage is commonly associated with aging and age-related diseases. In searching for cellular mechanisms in response to LMP, we used a proteomic approach to identify proteins enriched on damaged lysosomes. This unbiased approach identified a new phosphoinositide signaling pathway triggered by LMP to mediate rapid lysosomal repair. Specifically, LMP induces fast lysosomal recruitment of PI4K2A which generates high levels of the lipid messenger phosphatidylinositol-4-phosphate (PtdIns4P) on damaged lysosomes. Lysosomal PtdIns4P in turn recruits multiple oxysterol-binding protein (OSBP)-related protein (ORP) family members, including ORP9, ORP10, and ORP11, to orchestrate extensive membrane contact sites (MCSs) between damaged lysosomes and the endoplasmic reticulum (ER). The ORPs subsequently catalyze robust ER-to-lysosomal transport of phosphatidylserine (PS), which is critical for rapid lysosomal repair. The lipid transporter ATG2 is also recruited to damaged lysosomes, activated by PS, and is essential for rapid lysosomal repair. Our findings identify a phosphoinositide-dependent membrane tethering and lipid transport (PITT) pathway essential for the maintenance of lysosomal membrane integrity, with important implications for a wide range of diseases characterized by impaired lysosomal function.
HostingRepository	PRIDE
AnnounceDate	2022-09-07
AnnouncementXML	Submission_2022-09-07_08:54:32.423.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028852
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jay Tan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-29 13:59:25	ID requested
⏵ 1	2022-09-07 08:54:32	announced
2	2023-11-14 08:53:26	announced	2023-11-14: Updated project metadata.

10.1038/S41586-022-05164-4;

submitter keyword: Human, lysosomal membrane permeabilization

Jay X. Tan, PhD
contact affiliation	Aging Institute of UPMC Department of Cell Biology University of Pittsburgh School of Medicine Bridgeside Point I Room 457 100 Technology Dr. Pittsburgh, PA 15219
contact email	Jay.Tan@pitt.edu
lab head
Jay Tan
contact affiliation	University of Pittsburgh
contact email	Jay.Tan@pitt.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028852
     1. Label: PRIDE project
     2. Name: Proteins enriched on damaged lysosomes in 293T