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PXD043613 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells
DescriptionOxidative 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHossein Fazelinia
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-07 19:11:27ID requested
12023-07-19 07:49:46announced
22023-11-14 09:02:23announced2023-11-14: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: Oxidative stress, lysosome, age-related macular degeneration, aging, retina
Contact List
Joshua Dunaief, PhD, MD
contact affiliationAdele Niessen Professor of Ophthalmology Vice Chair for Research FM Kirby Center for Molecular Ophthalmology Scheie Eye Institute University of Pennsylvania
contact emailjdunaief@pennmedicine.upenn.edu
lab head
Hossein Fazelinia
contact affiliationChildren's Hospital of Philadelphia
contact emailfazeliniah@email.chop.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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