PXD043613

PXD043613 is an original dataset announced via ProteomeXchange.

Title	Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells
Description	Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration(AMD), the leading cause of blindness in the elderly, with retinal pigment epithelial (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured iPS-RPE cells increased lysosomal abundance, impaired proteolysis, and reduced the activity of a subset of lysosomal enzymes,including lysosomal acid lipase and acid sphingomyelinase. In a murine model of systemiciron overload, RPE cells accumulated lipid peroxidation adducts and lysosomes, developed progressive hypertrophy, and underwent cell death. Proteomic and lipidomic analyses revealed accumulation of lysosomal proteins, ceramide biosynthetic enzymes, and ceramides. The proteolytic enzyme cathepsin D had impaired maturation. A large proportion oflysosomes were galectin-3 positive, suggesting cytotoxic lysosomal membrane permeabilization (LMP). Collectively, these results demonstrate that iron overload induces lysosomal accumulation and impairs lysosomal function, likely due to iron-induced lipid peroxides that can inhibit lysosomal enzymes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:54:16.046.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-07 19:11:27	ID requested
1	2023-07-19 07:49:46	announced
2	2023-11-14 09:02:23	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:54:16	announced	2024-10-22: Updated project metadata.

10.1242/dmm.050066;

Zhang KR, Jankowski CSR, Marshall R, Nair R, M, á, s G, ó, mez N, Alnemri A, Liu Y, Erler E, Ferrante J, Song Y, Bell BA, Baumann BH, Sterling J, Anderson B, Foshe S, Roof J, Fazelinia H, Spruce LA, Chuang JZ, Sung CH, Dhingra A, Boesze-Battaglia K, Chavali VRM, Rabinowitz JD, Mitchell CH, Dunaief JL, Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells. Dis Model Mech, 16(7):(2023) [pubmed]

submitter keyword: Oxidative stress, lysosome, age-related macular degeneration, aging, retina

Joshua Dunaief, PhD, MD
contact affiliation	Adele Niessen Professor of Ophthalmology Vice Chair for Research FM Kirby Center for Molecular Ophthalmology Scheie Eye Institute University of Pennsylvania
contact email	jdunaief@pennmedicine.upenn.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2023/07/PXD043613

PRIDE project URI

• PRIDE
  1. PXD043613
     1. Label: PRIDE project
     2. Name: Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells