<<< Full experiment listing

PXD049336-2

PXD049336 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLysosomal storage disease proteo/lipidomic profiling using nMOST links ferritinophagy with mitochondrial iron deficiencies in cells lacking NPC2
DescriptionLysosomal storage diseases (LSDs) comprised ~50 gene loci causing the accumulation of cellular material in the lysosome and associated defects in lysosomal function, but systematic molecular phenotyping is lacking. Here, we apply a nanoflow-based multi-omic single-shot technology (nMOST) workflow to simultaneously quantify HeLa cell proteomes and lipidomes from dozens of LSD mutants, revealing diverse molecular phenotypes. Defects in delivery of ferritin and its autophagic regulator NCOA4 to lysosomes (ferritinophagy) were pronounced in NPC2-/- cells, which correlated with increased lyso-phosphatidyl-choline species and dramatic multi-lamellar membrane structures visualized by cryo-electron tomography. Ferritinophagy defects correlated with loss of mitochondrial cristae, MICOS complex components, and electron transport chain complexes rich in iron-sulfur cluster proteins. Strikingly, these defects were rescued when iron was provided through the transferrin system. This resource reveals how loss of lysosomal function impacts organelle homeostasis in trans and highlights nMOST profiling as a discovery tool for illuminating distinct molecular phenotypes across LSDs.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_07:00:56.163.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFelix Kraus
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-12 07:00:32ID requested
12024-10-08 10:49:39announced
22024-10-22 07:00:57announced2024-10-22: Updated project metadata.
Publication List
10.1101/2024.03.26.586828;
Kraus F, He Y, Swarup S, Overmyer KA, Jiang Y, Brenner J, Capitanio C, Bieber A, Jen A, Nightingale NM, Anderson BJ, Lee C, Paulo JA, Smith IR, Plitzko JM, Gygi SP, Schulman BA, Wilfling F, Coon JJ, Harper JW, Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST. bioRxiv, ():(2024) [pubmed]
Keyword List
submitter keyword: ferritinophagy,Multiplexed TMT proteomics, OXPHOS, lysosomal storage disorders, mitochondrial function
Contact List
J. Wade Harper
contact affiliationDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
contact emailwade_harper@hms.harvard.edu
lab head
Felix Kraus
contact affiliationHarvard Medical Sschool
contact emailfelix_kraus@hms.harvard.edu
dataset submitter
Full Dataset Link List
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/2024/10/PXD049336
PRIDE project URI
Repository Record List
[ + ]