PXD049336-2

PXD049336 is an original dataset announced via ProteomeXchange.

Title	Lysosomal storage disease proteo/lipidomic profiling using nMOST links ferritinophagy with mitochondrial iron deficiencies in cells lacking NPC2
Description	Lysosomal 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_07:00:56.163.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Felix Kraus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-12 07:00:32	ID requested
1	2024-10-08 10:49:39	announced
⏵ 2	2024-10-22 07:00:57	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: ferritinophagy,Multiplexed TMT proteomics, OXPHOS, lysosomal storage disorders, mitochondrial function

J. Wade Harper
contact affiliation	Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
contact email	wade_harper@hms.harvard.edu
lab head
Felix Kraus
contact affiliation	Harvard Medical Sschool
contact email	felix_kraus@hms.harvard.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/2024/10/PXD049336

PRIDE project URI

• PRIDE
  1. PXD049336
     1. Label: PRIDE project
     2. Name: Lysosomal storage disease proteo/lipidomic profiling using nMOST links ferritinophagy with mitochondrial iron deficiencies in cells lacking NPC2