{"database":"MassIVE","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/v08/MSV000095985/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["J. Wade Harper","Joshua J. Coon"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=f62ccca1184a405085bceb42f48e3ebf"],"submitter_email":["wade_harper@hms.harvard.edu","jcoon@chem.wisc.edu"],"sample_protocol":[""],"repository":["MassIVE"],"file_size":["2,754"],"ptm_modification":["MS:1002864 - No post-translational-modifications are included in the identified peptides of this dataset"],"data_protocol":[""],"omics_type":["Proteomics"],"instrument_platform":["Orbitrap Astral"],"species":["Homo Sapiens (ncbitaxon:9606)"],"submitter_affiliation":["University of Wisconsin-Madison","Harvard Medical School - Dpt of Cell Biology"],"pubmed_abstract":["Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multiomic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in <i>NPC1</i><sup>-/-</sup> and <i>NPC2</i><sup>-/-</sup> mutants, where lysosomes accumulate cholesterol. Autophagic and endocytic cargo delivery failures correlated with elevated lysophosphatidylcholine species and multilamellar structures visualized by cryo-electron tomography. Loss of mitochondrial cristae, MICOS complex components, and OXPHOS components rich in iron-sulfur cluster proteins in <i>NPC2</i><sup>-/-</sup> cells was largely alleviated when iron was provided through the transferrin system. This study reveals how lysosomal dysfunction affects mitochondrial homeostasis and underscores nMOST as a valuable discovery tool for identifying molecular phenotypes across LSDs."],"pubmed_title":["Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST."],"pubmed_authors":["Kraus Felix F, He Yuchen Y, Swarup Sharan S, Overmyer Katherine A KA, Jiang Yizhi Y, Brenner Johann J, Capitanio Cristina C, Bieber Anna A, Jen Annie A, Nightingale Nicole M NM, Anderson Benton J BJ, Lee Chan C, Paulo Joao A JA, Smith Ian R IR, Plitzko Jürgen M JM, Gygi Steven P SP, Schulman Brenda A BA, Wilfling Florian F, Coon Joshua J JJ, Harper J Wade JW"],"name_synonyms":["nuclear pore membrane protein, malignant neoplasm of anterior wall of nasopharynx, malignant neoplasm of lateral wall of nasopharynx, CDF, ammonium ferric citrate., malignant tumor of lateral wall of nasopharynx, nasopharyngeal cancer, Desmoplastic astrocytoma of infancy, malignant neoplasm of superior wall of nasopharynx, total expressed protein, LFQ, CG1768, malignant neoplasm of roof of nasopharynx, DRF2, ms(2)04138, Desmoplastic infantile astrocytoma, POF, malignant nasopharyngeal tumour, E381, malignant tumour of posterior wall of nasopharynx, cancer of nasopharynx, DmelCG1768, MLPLI, malignant nasopharyngeal tumor, HILDA, malignant neoplasm of nasopharyngeal wall, malignant neoplasm of nasopharynx (disorder) [ambiguous], AGAMOUS-like 61, Dias, nucleopore, DiA, NPC, ammonium iron(III) citrate, l(2)k07135, nuclear pore complex, malignant tumor of posterior wall of nasopharynx, POF2, F27C12_24, F27C12.24, nasopharyngeal throat cancer, primary malignant neoplasm of anterior wall of nasopharynx, malignant tumor of anterior wall of nasopharynx, DIASP, FerriSeltz, DIA, Dia, malignant neoplasm of nasopharynx, 4-(4-dihexadecylaminostyryl)N-methylpyridium iodide, nasopharyngeal carcinoma, cancer of the nasopharynx, Npca, malignant tumour of lateral wall of nasopharynx, malignant neoplasm of posterior wall of nasopharynx, DIANA, 38E.16, Mouse Neural Progenitor cell line, malignant neoplasm of other specified sites of nasopharynx, malignant tumour of anterior wall of nasopharynx, DIA2, Proteomes"],"description_synonyms":["Therapy, CDF, fac, Effects, 2700012J19Rik, ammonium ferric citrate, DmelCG4609, Desmoplastic astrocytoma of infancy, postnatal development, Longterm Effect, total expressed protein, LFQ, growth and development, CG1768, CT22505, DRF2, Long Term, BcDNA:GH22047, development, ms(2)04138, Desmoplastic infantile astrocytoma, EDDM1, disease management., POF, Experiment, E381, clone 1.34, Genogroup, DmelCG1768, MLPLI, Long Term Effects, HILDA, AGAMOUS-like 61, NPC1, NPC2, Dias, Effect, CG4609, DiA, BcDNA:RH53228, NPC, CG7291, treatment, ammonium iron(III) citrate, l(2)k07135, anon-WO0172774.63, anon-WO0172774.66, dnpc2a, Longterm, anon-WO0172774.65, POF2, anon-WO0172774.62, F27C12_24, F27C12.24, postnatal growth, npc2a, DmelCG7291, anon-WO0172774.68, HE1, anon-WO0172774.67, anon-WO0172774.69, anon-EST:Liang-1.34, Long-Term, DIASP, FerriSeltz, FA3, DmML3, BEST:GH08376, Treatments, DIA, Dia, Longterm Effects, Genotypes, 4-(4-dihexadecylaminostyryl)N-methylpyridium iodide, Genogroups, AU045843, FAC, Therapeutic, DIANA, 38E.16, Therapies, AA408070, Treatment, Long-Term Effect, DIA2, growth, time point, Proteomes, Long-Term Effects, FACC, Fax"],"pubmed_title_synonyms":["Lipidome, Disease, Lysosomal Enzyme, Disorders, phospholipidosis, Lysosomal Enzyme., Enzyme Disorders, Lysosomal Enzyme Disorders, Enzyme Disorder, Lysosomal, Disorder, Lysosomal Enzyme Disorder, Lipidomic, Diseases, \"disorder of lysosomal enzyme (disorder)\" EXACT [SNOMEDCT_2005_07_31:23585005], Lysosomal Storage, Lipidomes, Lysosomal Storage Disease, \"inborn lysosomal enzyme disorder\" EXACT [CSP2005:1849-5878]"],"pubmed_abstract_synonyms":["l(2)k04204, mitochondrial contact site and cristae organizing system, Electron Tomography, Disorders, ER-Phagy, FON1, Lipidomic, N-diethyl-6-methyl-, DNase gamma, Lysophosphatidylcholine, Globulin, LSD-25, 6330543G17Rik, Autolysosome, Tomography, sci, congenital defects, FLORAL ORGAN NUMBER 1, cargo, aplasia, MitOS complex, EDDM1, EM Tomography, Liver regeneration-related protein LRRG03, diseases, SUP, CG9063, 17alpha)-cholest-5-en-3-ol, HOW, How, diseases and disorders, 26Fe, Work Flow, 9, 14beta, l(3)j5D5, MINOS complex, 24B, beta 2 Transferrin, human disease, (3beta, Moods, Bdr, Su(Mir)1, hypoplasia, stru, Cholest-5-en-3beta-ol, l(3)S053606, Super protein, inhibition of homeostatic process, BcDNA:GH03694, CG10293, sp, SNAP-25, Epicholesterol, DNAS1L3, l(3)j5B5, Fcj1 complex, ER Phagy, Nucleophagy, AA408070, homeostasis, Homo sapiens disease, l(2)CA4, Lysosomal Storage Disease, Prx3, DmelCG9063, Ergoline-8-carboxamide, TEM Tomography, 3.1.21.-, 10-didehydro-N, Transferrin, 0904/17, Microscope Tomography, OXPHOS, Lysergic Acid, Electron Microscope, tau Transferrin, Arts, Lysosomal Storage, cristae, mitochondrial cristae, beta-1, Ribophagy, CT22505, Scanning Transmission Electron Microscopy Tomography, MIB complex, Autolysosomes, deformities, shortstop/kakapo, Isotransferrin, Workflows, Iron 56, (8beta)-, EM, ATP synthase D chain, positive regulation of homeostatic process, SLEB16, Reticulophagy, SZ1, DmelCG18076, Lipid, Diseases, Autophagocytosis, Cellular, GENA70, Liver and spleen DNase, Electron Microtomography, tau-Transferrin, longitudinal data analysis, NPC, Lysolecithin, Transmission Electron, atresia, Mitofilin complex, Mitochondrial, Industrial, beta-1 Metal-Binding Globulin, Industrial Arts, Grv, Iron, Autophagy, BcDNAGH03694, malformations, lysophosphatidylcholines, Transferrins, beta 1 Metal Binding Globulin, Transferrin C, HE1, Transferrin B, Electron, DmML3, SHOT, 3L6, Metal-Binding Globulin, Fe, disease, Lysergic, Lipidome, Eisen, AU045843, rich, grv, Enzyme Disorder, Lysosomal Enzyme Disorder, anomalies, Cells, STEM, monoacylglycero-3-phosphocholine, anon-EST:Liang-2.39, Serotransferrin, iron, 42/4, Proteomes, Work Flows, FLORAL DEFECTIVE 10, lipids, other disease, OG12X, Lysosome, Enzyme Disorders, Lysergide, Lysosomal Enzyme Disorders, P62, Gene, Lipophagy, SUPERMAN, Monoferric Transferrins, mitochondrial, BcDNA:GH22047, PRO1400, l(2)k05821, l(2)k15606, Cholest-5-en-3-ol (3beta)-, Gene Products, disease or disorder, Cellular Autophagy, Deoxyribonuclease I-like 3, Mood, defects, Shot, BcDNA:RH53228, study, hierro, DHP2, anatomical systems, l(2)k10821, Transmission, l(3)s2612, Lysosomal, Siderophilin, dysfunction, HeLa, npc2a, DmelCG7291, BEST:GH08376, non-neoplastic, Mif1, Disorder, Diethylamide, DmelCG10293, negative regulation of homeostatic process, disorder, species, Transmission Electron Microscopy Tomography, Monoferric, Acid Diethylamide, Autoregulation, Disease, Trf, 2700012J19Rik, clone 2.39, kop, Affects, Proteins, disorders, Phenotypes., CG18076, Lipidomes, fer, medical condition, selective autophagy, Synaptosomal-associated 25 kDa protein, CG18637, qkr, l(3)S090417, LSD, Cell, Beta-1 metal-binding globulin, Lysosomal Enzyme, HeLa Cell, agenesis, KH93F, Protein, STEM Tomography, beta 2-Transferrin, condition, NPC1, NPC2, HELA cell, Cholesterin, regulation of homeostatic process, DNase I homolog protein DHP2, who, CG7291, l(2)k05434, ferrum, LSD 25, LS-DNase, dnpc2a, Transmission Electron Microtomography, l(2)k03010, kak, FLO10, Who/How, pathophysiology, Iron-56, DNase I-like 3, HERP, OG12, beta-1 Metal-Binding, Protein Gene Products, Gene Proteins, Lysolecithins, activation of homeostatic process, Microtomography, Lysergic Acid Diethylamide Tartrate, SNAP, birth defects, qkr[93F], Og12x, TEM"],"additional_accession":["PXD056356"]},"is_claimable":false,"name":"LFQ DIA to analyze the proteome of NPC mutant iNeurons with and without ferric ammonium citrate","description":"Label-free quantification (LFQ) using data-independent acquisition (DIA) on the Orbitrap Astral was performed to analyze the proteome of iNeurons with NPC1 and NPC2 knocked out. The experiment includes the following time points of development: day 0, 4, 8, 16, and 22. All samples were cultured in regular media, with or without ferric ammonium citrate (FAC), and processed in triplicates for each time point, genotype, and treatment.","dates":{},"accession":"MSV000095985","cross_references":{"pubmed":["39841834"]}}