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Gielisch"],"technology_type":["SRM/MRM","Mass Spectrometry","Shotgun proteomics"],"disease":["Osteosarcoma"],"software":["Not available"],"submitter_keywords":["Oxphos deficiency","Ubiquitination","Retrograde response","Metabolome profiling","Proteome profiling","Ρ0 cells","Mass spectrometry"],"full_dataset_link":["http://www.ebi.ac.uk/pride/archive/projects/PXD002425"],"tissue":["Permanent Cell Line Cell","Bone Marrow"],"sample_protocol":["The osteosarcoma cell line 143B.TK- (ATCC-CRL-8303) was obtained from LGC Standards and was the parental line of recently generated ρ0 cells. The wild-type cell line 143B.TK- and the according ρ0 cells were cultivated in SILAC DMEM (Silantes, Munich, Germany, without L-lysine and L-arginine) containing 4.5 g/L glucose, 1 mM pyruvate, supplemented with 5% dialyzed FBS (Silantes, Munich, Germany), 1% Penicillin-Streptomycin-Neomycin (Invitrogen, Carlsbad, USA), 100 µg/mL bromodeoxyuridine (Sigma-Aldrich, St. Louis, USA) and 50 µg/mL uridine (Sigma-Aldrich, St. Louis, USA) at 37 °C in a humidified atmosphere of 5% CO2. Cells were labeled with light (L) or heavy (H) isotopes of arginine (12C614N4, 13C615N4; 30 mg/L) and lysine (12C614N2, 13C615N2; 80 mg/L; both: Silantes, Munich, Germany) and grown to confluency in one 300 cm2 polystyrene flask per replicate. Proteomic experiments were done in biological quadruplicates, including a label-switch. For metabolome profiling and enzymatic measurements, light SILAC labeled cultures were grown in biological triplicates.
Sample processing details for metabolite and protein profiling are available at PMID: (upon publication)"],"repository":["Pride"],"quantification_method":["SILAC"],"modification":["ubiquitination signature dipeptidyl lysine","phosphorylated residue"],"data_protocol":["The proteomics data were analyzed with the MaxQuant data analysis workflow version 1.5.0.0 with the Andromeda search engine. The False Discovery Rate (FDR) was set to 1% for protein, peptide spectrum match and site decoy fraction level. Tryptic peptides were required to have a minimum length of 7 amino acids and a maximum of two missed cleavages. MaxQuant was used to score fragmentation scans for identification based on a search with an allowed mass deviation of the precursor ion of up to 4.5 ppm after time dependent mass calibration. The allowed fragment mass deviation was 20 ppm. Fragmentation spectra were searched by Andromeda in the human proteome database UniProtKB with 88.717 entries, released in 11/2014, combined with common contaminants. Carbamidomethylation of cysteine was set as fixed modification and N-terminal protein Acetylation and Oxidation (M) as variable modifications for the total cell lysates; additionally Phospho (STY) and GlyGly (K) were set as variable modification for the according enriched samples. Further downstream analysis of the results was performed with String, GSEA, Enrichr, Perseus and Prism, according to our publication.
Relative quantification of the metabolomics data was performed using MultiQuantTM software v.2.1.1. Integration settings were a Gaussian smooth width of 2 points and a peak splitting factor of 2. Peak integrations were reviewed manually and normalized according to the protein content and subsequently by internal standards. The average of all MRM ion ratios per metabolite was used for relative quantification between sample cohorts."],"omics_type":["Proteomics"],"labhead":["David Meierhofer"],"instrument_platform":["Q Exactive"],"labhead_affiliation":["Max Planck Institute for Molecular Genetics, Ihnestrasse 63-72, 14195 Berlin, Germany"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["gielisch@molgen.mpg.de"],"publication":["26852163 Gielisch I, Hardt C, Wittig I, Meierhofer D. An impaired respiratory electron chain triggers down-regulation of the energy metabolism and de-ubiquitination of solute carrier amino acid transporters. Mol Cell Proteomics. 2016 Feb 6. pii: mcp.M115.053181"],"curator_keywords":["Biological","Biomedical"],"submitter_affiliation":["MPIMG"],"pubmed_abstract":["Hundreds of genes have been associated with respiratory chain disease (RCD), the most common inborn error of metabolism so far. Elimination of the respiratory electron chain by depleting the entire mitochondrial DNA (mtDNA, ρ(0) cells) has therefore one of the most severe impacts on the energy metabolism in eukaryotic cells. In this study, proteomic data sets including the post-translational modifications (PTMs) phosphorylation and ubiquitination were integrated with metabolomic data sets and selected enzyme activities in the osteosarcoma cell line 143B.TK(-) A shotgun based SILAC LC-MS proteomics and a targeted metabolomics approach was applied to elucidate the consequences of the ρ(0) state. Pathway and protein-protein interaction (PPI) network analyses revealed a nonuniform down-regulation of the respiratory electron chain, the tricarboxylic acid (TCA) cycle, and the pyruvate metabolism in ρ(0) cells. Metabolites of the TCA cycle were dysregulated, such as a reduction of citric acid and cis-aconitic acid (six and 2.5-fold), and an increase of lactic acid, oxalacetic acid (both twofold), and succinic acid (fivefold) in ρ(0) cells. Signaling pathways such as GPCR, EGFR, G12/13 alpha, and Rho GTPases were up-regulated in ρ(0) cells, which could be indicative for the mitochondrial retrograde response, a pathway of communication from mitochondria to the nucleus. This was supported by our phosphoproteome data, which revealed two main processes, GTPase-related signal transduction and cytoskeleton organization. Furthermore, a general de-ubiquitination in ρ(0) cells was observed, for example, 80S ribosomal proteins were in average threefold and SLC amino acid transporters fivefold de-ubiquitinated. The latter might cause the observed significant increase of amino acid levels in ρ(0) cells. We conclude that an elimination of the respiratory electron chain, e.g. mtDNA depletion, not only leads to an uneven down-regulation of mitochondrial energy pathways, but also triggers the retrograde response."],"pubmed_title":["An Impaired Respiratory Electron Chain Triggers Down-regulation of the Energy Metabolism and De-ubiquitination of Solute Carrier Amino Acid Transporters."],"pubmed_authors":["Aretz Ina I, Hardt Christopher C, Wittig Ilka I, Meierhofer David D"],"view_count":["570"],"pubmed_abstract_synonyms":["projections, F14G24.19, dlmo, Materials, DLMO, H3cit, Ass-1, Metabolisms, fond, Elp-B1, der, 2-Hydroxy-, F14G24_19, Elp-1, alpha-Spe, Errb1, Ribosomal Protein, Metabonomics, CycEI, Mitochondrial Contractions, Downregulation, alpha-Spc, CG31654, phosphorylation, PIG61, dmTAF[[II]]230, Receptor Mediated Signal Transduction, protein polypeptide chains, dLmo, dLMO, Personal, Communications, epidermal growth factor-activated receptor activity, metabolic hereditary disorder, fold, 1, RCD, 2, Expenditure, AAF01186, Cell Signaling, Ammonium Succinate, Dmrho, average, amino acids, VTS20631, TFIID TAF250, cel, Dm-OAMB, Personnel, DMRHO, GALR4, beta-particle, Pathways, proteins, L Lactic Acid, flb, Social, DmelCG8416, Bd, mitochondrial signaling pathway, e, ch, e-, hFz4, Dlmo, GALRL, 9030024J15Rik, Homo sapiens disease, R-RCD1, GM05887A, Signal Transduction Pathways, fliH, pyruvate metabolism, 5-dioic acid, single organism signaling, Sarcolactic Acid, CG3856, retrograde response, dTAF[[II]]230, Pathway, anatomical protrusion, Citrate, Elp, Rho-1, FZD4S, DEgfr, Krebs cycle, acid, TAF200, CG1004, G protein coupled receptor, Normalcy, Potassium Succinate, Cyc E, alpha-amino carboxylic acids, signal transduction by trans-phosphorylation, ada, FzE4, torpedo/egfr, OAMB-1a, cytoskeletal regulator activity, D-Ada, Dmoa1, BG:DS07108.3, LACTIC ACID, shelf, PCD, dAP-2a, l(2)05206, RHOHP1, D Lactic Acid, ParaT, egfr, l(2)06694, Acid, cytoskeleton organisation, 4 Butanedioic Acid, HD-33, El, Amino acids, AI326383, D-Rho1, D-Milchsaeure, Anhydrous Citric Acid, EGFR, DER/EGFR, EGfr, EgfR, congenital metabolic disorder, DER flb, alpha, AP-2alpha, RHO, Rho, Torpedo/Egfr, projection, ridge, DmelCG4260, beta(-), Degfr, inherited disorders of metabolism, CCL21, signaling pathway, Taf250, rhomboid/veinlet, Material, DEGFR, SCYA21, Cells, l(2)05351, ARHD, Acids, rho, (2R)-2-hydroxypropanoic acid, TAF230, Eukaryotic, RCB2862, anon-EST:fe2E2, cycline, D-Egf, cytoskeletal organization and biogenesis, proto-oncogene c-ErbB-1, inborn error of metabolism, Peptidomics, SLC, lamellae, DmcyclinE, 2 Hydroxypropionic Acid, alpha-Spect, e(-), Arhd, Kern, mENA, protein-containing complex, EK2-6, process of organ, Propanoic Acid, fs(3)neo61, cdi7, CITRIC ACID, lamella, CG10422, Signal Transduction, (2S)-, cyclinE, EGFr, Egfr, regulated cell death, Cdi7, CDI7, Mitochondrion, disease or disorder, torpedo/Egfr, TOP, Misinformations, CG6500, nucleo atomico, respiratory chain, DmOAMB, DmOctalpha1Rb, Normalities, dRhoA, Bcl-10, dTAF[[II]]250, beadex/dLMO, Butanedioic Acid, cell, Contraction, Elektron, Signal, dre3, Energy, Ammonium Lactate, top, retrograde response., Signal Pathways, Expenditures, DmcycE, Alpha-Adaptin, Signal Transduction Pathway, Ccl21c, dTAF250, RhoHP1, Citric acid, Ccl21b, 2-Hydroxytricarballylic acid, dRho1, Saeure, laminae, Signal Pathway, inborn disorders of metabolism, Anhydrous, inborn metabolic disorder, Potassium, l(3)dre3, Elp-B1RB1, DmelCG6500, Rho kinase, metabolic energy generation, alpha-Spectrin, Mitochondrial DNA, (-)-lactic acid, TGF-alpha receptor activity, ERBB, dEGFR1, l(2)52Fa, anatomical process, Proteins, disorders, Phosphorylations, Receptor-Mediated Signal Transductions, BG:DS00004.13, alpha-amino acids, Cell, Down Regulation, dTAF230, Down-Regulation, l(2)k02514, native protein, DmCycE, Down-Regulation (Physiology), Communications Personnel, TAF[[II]]250/230, condition, MENE(2L)-A, DER/top, signalling cascade, alphaSp, Fz-4, dnRho, organ process, Energy Expenditure, inborn errors of metabolism, Taf[[II]]250, Fz4, B-cell CLL|lymphoma 10, l(2)k02602, mating_type_alpha, SNSR6, Saeuren, SNSR4, Oamb a, Oamb b, Energy Expenditures, E3.10/J3.8, nucleus of neuraxis, wa-2, 3-propanetricarboxylic acid, neuraxis nucleus, beta, signalling, Miscommunications, Eukaryotic Cell, D-CycE, processes, AP2, (2R)-, signalling process, G-PROTEIN COUPLED RECEPTOR 2, Bam-C, Erbb, alpha mating type (yeast), Receptor, MRGX1, UNQ784/PRO1600, 2-Ethanedicarboxylic Acid, MRGX4, DER/faint little ball, D-2-Hydroxypropanoic acid, L-Lactic Acid, Signal Transductions, BamF, AP-2, BamC, caspase-independent cell death, Rho A, Aminosaeure, GM05887, Metabonomic, Amino acid, Bioenergetics, D-Lactic Acid, protein, Atomkern, hdp-a, l(3)04276, Succinate, DmelCG1004, Ccne, diseases, rho-1, AA408052, AI552599, horsetail nucleus, alpha-adaptin, diseases and disorders, DRho, Miscommunication, DmelCG10422, protein aggregate, d-egf-r, 8416, CD344, alpha-spec, signal transduction by protein phosphorylation, neuronal nucleus, nucleus atomi, opsin-2, Ribosomal, human disease, Ubiquitylation, PPI, mitochondrial genome, CG4260, 2 Ethanedicarboxylic Acid, (R)-(-)-lactic acid, 2-Hydroxypropionic Acid, 4-Butanedioic Acid, secondary lymphoid-tissue chemokine, 2-Hydroxy-1, Social Communications, nonapoptotic programmed cell death, alpha-spectrin, rhoA, Rho1, RHO1, Communication, ASS, HOS-143b, beta chemokine exodus-2, signaling process, papilla, rho1, intermediary metabolism, D-EGFR, ubiquitination, Transductions, 2610009E16Rik, associated, PGR7, NISBD2, DER1, DmRHO-A, Wa5, l(2)09261, OAMB-AS, Social Communication, Aminokarbonsaeure, Citric Acid Monohydrate, RHOb, lamina, 2-hydroxypropane-1, signal transduction by conformational transition, HSC0013, flanges, ham, rare inborn errors of metabolism, TAFII-250, TAF250/230, br37, Citric Acid, CG10079, Dm Rho1, Programs, rhom, Program, alphaSpec, signaling cascade, TAFII250, RhoN19, Receptor Down-Regulation, D-2-Hydroxypropionic acid, wa2, cytoskeleton organization and biogenesis, RhoA, Diseases, cg4260, ve, EVR1, Genetic Materials, RHOM, RhoM, cell nucleus, spectrin, Transduction, Genetic Material, MENE (2L)-A, Ptd, mitochondria-nucleus signal transduction, Amino Acid, OAMB, Mitochondrial, DmelCG3856, acide, shelves, System, Ve, 2-Hydroxypropanoic Acid, dEgfr, inherited metabolic disorder, CG8416, acids, common, oamb, acido, CG17603, TAF[[II]], DMRHOa, DMRHOb, pre-pulse inhibition, disease, Energy Metabolisms, Health, TCA4, mitochondrial DNA, l35Dd, spine, SR3-5, l(2)57DEFa, Lmo, LMO, caspase-independent apoptosis, Cistron, dEGFR, hdp, Communication Program, 3-tricarboxylic acid, DmHD-33, D-Lactic acid, Ammonium, receptor tyrosine-protein kinase erbB-1, Misinformation, thymus-derived chemotactic agent 4, other disease, Dmelrho, Signal Transduction Systems, alpha-Ada, d230, biological signaling, small-inducible cytokine A21, noyau atomique, l(3)alpha-Spec, DRORHO, C-erb, Receptor-Mediated, Aminocarbonsaeure, congenital metabolism disorder, mor1, Gene, dTAFII250, Signal Transduction System, cycE, electron, alpha-amino acid, mitochondrial signalling pathway, EfW1, pyruvate dehydrogenase bypass, l(2)br37, l(2)SH2 0460, Rho GTPase, CYCLE, protrusion, osteoblastic sarcoma cell line, alpha-ada, polypeptide chain, DRhoA, dmTAF1, Taf230, Metabolism, dttg, c-erbB, klo, citric acid cycle, EGF receptor activity, non-apoptotic programmed cell death, alpha-Sp, Egf-r, energy pathways, Metabolomic, CG1977, GPCR, TAF250, inborn metabolism disorder, nuclei, study, Taf200, EGF-R, CYCE, Genetic, E330, DmelCG3938, CyclE, nucleus of CNS, noyau, nucleo, 3938, membrane electron transport chain, Taf1p, Torpedo/DER, ridges, DRho1, top/flb, DrhoA, non-neoplastic, OPN2, l(2)k05007, Communication Programs, dm-cycE, signalling pathway, nucleus, l(2)57EFa, Drho1, disorder, signal transduction by cis-phosphorylation, l(2)57Ea, OctR, TAF, CG15698, Personal Communication, data, Lactate, TAF[[II]]250, 2 Hydroxypropanoic Acid, DmOCT1B, 3A9, protein complex, DmelCG1977, iks, l(3)84Ab, small-inducible cytokine A21c, small-inducible cytokine A21b, medical condition, small-inducible cytokine A21a, OctR1, l(2)k02107b, Citronensaeure, Cistrons, FEVR, Contractions, epidermal growth factor receptor activity, natural protein, DmelCG10079, nervous system nucleus, p230, Receptor-Mediated Signal Transduction, Protein, Systems, D-lactic acid, TFIID, CyeE, inherited disorder of metabolism, osteogenic sarcoma cell line, flange, OAMB-K3, Uralyt U, mtDNA, 143B, TAF[[II]]230, D-alphaAda, negatron, top/DER, Normality, 3-Carboxy-3-hydroxypentane-1, l(2)35Dd, FCP-B, TAF[II]250, ERBB1, Amino, GCR2, Bioenergetic, Mitochondrial Contraction, hld, Scya21b, process, Egf, DmelCG17603, TCA cycle, EFG-R, mitochondria, Scya21c, Errp, l(3)62Bd, 6Ckine, BAM, Bam, Der, DER, l(2)SH0460, rare inherited metabolic disorder, alfa-Spec, processus, transforming growth factor-alpha receptor activity, rare metabolic disease, hereditary metabolic disease, CG3938, n(2)k07236, DER/torpedo, Spec, HER1, TAF1"],"data_synonyms":["IPP2A2, ion, determination, Aminosaeure, Metabonomic, Amino acid, Metabonomics, protein, STY, Sty, composed of, Long Term, binding site, 5730420M11Rik, peptide, dmTAF[[II]]230, Polypeptides, protein polypeptide chains, primary metabolites, ClvPrd, peptido, DmelCG1921, Software Engineering, Analysis, Work Flow, protein aggregate, sty, Effect, WMS, Computer Program, average, SET, F, amino acids, peptides, TFIID TAF250, Analyses, TAF-I, cel, phosphatase 2A inhibitor I2PP2A, Open, CLK|STY, Computer Programs and Programming, composition, proteins, arg, DmelCG4299, dSPRY, set, IGAAD, DmelCG10574, ppm, Half Cystine, GPHYSD2, Long-Term Effects, SGS, ratio, phapii, dTAF[[II]]230, Zinc Cysteinate, T5E21.12, Aminokarbonsaeure, Longterm Effect, TAF200, StF-IT-1, Search, Normalcy, TAFII-250, TAF250/230, alpha-amino carboxylic acids, results, Source Softwares, CG1921, Software Tools, ACMICD, Programs, Multiple Reaction Monitoring, Program, Computer Applications, Workflows, TAFII250, Ionen, Computer Applications Software, Computer Applications Softwares, Softwares, region, T5E21_12, Gm92, parent ion, Amino Acid, Acid, Software Applications, HLA-DR-associated protein II, positional polypeptide feature, Amino acids, DI-2, Source Software, I-2Dm, content, proportionality, common, rate, L-Cysteine, CG4299, MASS, inhibitor of granzyme A-activated DNase, CG17603, TAF[[II]], human, I-2PP1, sample., Applications, Health, TAF-IBETA, precursor ion, Taf250, SR3-5, metabolites, TAF-Ibeta, Acids, Polypeptide, i2pp2a, time, Proteomes, Work Flows, TAF230, Computer Software Applications, CLK, breadth, d230, criteria, human being, Cysteine Hydrochloride, Peptidomics, False, region or site annotation, Effects, Aminocarbonsaeure, FBN, secondary metabolites, dTAFII250, alpha-amino acid, precursor, Computer, guidelines, protein-containing complex, EfW1, PHAPII, period, l(3)rQ526, template-activating factor I, polypeptide chain, Publication, dmTAF1, ECTOL1, Taf230, Half-Cystine, Metabolomic, l(3)j5E11, Application, TAF250, Normalities, Open Source Softwares, Search Engines, proportion, positional, Taf200, dTAF[[II]]250, MRM, Longterm, cell, L Cysteine, Software Application, iones, protein amino acid acetylation, ipp2a2, spry, Argos, Open Source Software, 2pp2a, Taf1p, CG4531, Long-Term, ions, man, CG10574, Computer Software Application, OCTD, dTAF250, 2PP2A, 10^[-6], Tools, taf-ibeta, DmAos, dSET, dSet, site, peptidos, Long-Term Effect, TAF, rlt, CS3-3, Applications Software, Open Source, data, TAF[[II]]250, Computer Software, protein complex, igaad, total expressed protein, l(3)84Ab, alpha-amino acids, BG:DS00004.13, compositionality, Peptide, Cell, Engine, Tool, dTAF230, polypeptide, CLK/STY, Spry, l(3)rJ812, Software Tool, native protein, natural protein, I-2PP2A, p230, PRISM, Dm I-2, Protein, Long Term Effects, chemical analysis, I2PP2A, TAF[[II]]250/230, TFIID, MFS1, l(3)05959, Software, WMS2, Taf[[II]]250, TAF[[II]]230, gil, Normality, INSDC_feature:misc_binding, SRM, Engineering, metabolite, TAF[II]250, Amino, Sry, l(3)05845, sample population, Longterm Effects, smooth, DmelCG4531, Computer Programs, dSET/TAF-Ibeta, Aos, 2610030F17Rik, DmelCG17603, Applications Softwares, binding_or_interaction_site, Ion, Data, SSKS, l(3)rJ472, structure, Calibrations, quotient, Peptid, assay, variable, AA407739, Data Analyses, TAF1"],"name_synonyms":["Metabolisms, Aminokarbonsaeure, e(-), Aminocarbonsaeure, Amino acid, impaired, Bioenergetics, alpha-amino acids, electron, alpha-amino acid, Downregulation, alpha-amino carboxylic acids, Down Regulation, partial functionality, dysfunctional, Down-Regulation, Receptor Down-Regulation, Down-Regulation (Physiology), Metabolism, Expenditure, Energy Expenditure, Amino Acid, Acid, Ubiquitylation, amino acids, negatron, Amino acids, dysfunction, Elektron, Energy Expenditures, beta-particle, Energy, lacks function of type, Expenditures, Amino, low functionality, beta, Bioenergetic, beta(-), Aminosaeure., having decreased function, e, ch, Energy Metabolisms, e-, carrier, Acids, Receptor, ubiquitination"],"pubmed_title_synonyms":["Metabolisms, Aminokarbonsaeure, e(-), Aminocarbonsaeure, Amino acid, impaired, Bioenergetics, alpha-amino acids, electron, alpha-amino acid, Downregulation, alpha-amino carboxylic acids, Down Regulation, partial functionality, dysfunctional, Down-Regulation, Receptor Down-Regulation, Down-Regulation (Physiology), Metabolism, Expenditure, Energy Expenditure, Amino Acid, Acid, Ubiquitylation, amino acids, negatron, Amino acids, dysfunction, Elektron, Energy Expenditures, beta-particle, Energy, lacks function of type, Expenditures, Amino, low functionality, beta, Bioenergetic, beta(-), Aminosaeure., having decreased function, e, ch, Energy Metabolisms, e-, carrier, Acids, Receptor, ubiquitination"],"sample_synonyms":["CRL3, Fanconi syndrome with intestinal malabsorption and galactose intolerance, Lysine Hydrochloride, L-arginine, DL-Arginine Acetate, Glukose, 5 Bromo 2' deoxyuridine, GM05887, A4, NSC-38297, Monohydrate, Visible Light, Profiles, protein, (DL)-Isomer, BUdR, Publication., dmTAF[[II]]230, protein polypeptide chains, Lysine Acetate, primary metabolites, Bromouracil, Streptomycin Sulfate, CRUMPLED LEAF, Dextrose, hnu, Line, 2, GSD due to GLUT2 deficiency, Arg, protein aggregate, foton, 1-beta-D-ribofuranosylpyrimidine-2, Uridin, L Lysine, Penicillin Antibiotics, Metabolic Profiles, O-2-deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5-deoxy-3-C-formyl-alpha-L-lyxofuranosyl-(1-4)-N, (S)-2-amino-5-guanidinopentanoic acid, TFIID TAF250, Allo-Uridine, cel, N'-bis(aminoiminomethyl)-, K, (S)-2-Amino-5-guanidinovaleric acid, R, epsilon-diaminocaproic acid, Arginine, Monohydrate DL-Arginine Acetate, proteins, DL-glucose, glucose, Strepto-Hefa, HOS-143b, LYS, Lysin, sample, GM05887A, u, 2-oxopropanoic acid, gamma, L-Arginin, GPL, dTAF[[II]]230, Radiation, Arginine Hydrochloride, PLCA2, TAF200, arginine, Light, Penicillin, TAFII-250, TAF250/230, glycogen storage disease 11, IL-31RA, Deoxyriboside, PRO21384, TAFII250, g/L, LIGHT, Streptomycin Sulphate, lysine, 1-beta-D-ribofuranosyluracil, Streptomycine Panpharma, Arnold-Chiari malformation, Bickel-Fanconi glycogenosis, (alpha-D)-Isomer, Uridine, Estreptomicina Normon, Lines, L-Arginine, Visible Radiations, D-Glucose, glycogenosis due to GLUT2 deficiency, glycogen storage disease due to GLUT2 deficiency, Visible Radiation, HVEML, URIDINE, glycogenosis Fanconi EXACT, DMEM, alpha, CG17603, TAF[[II]], Fanconi-Bickel syndrome, Neomycin Sulfate, 5-Bromo-2'-deoxyuridine, Atmospheres, DMDA, light quantum, Chiari type II malformation, hepatic glycogenosis with amino aciduria and glucosuria, Arnold-Chiari malformation type II, Taf250, Cm2, D Glucose, SR3-5, pyruvate, metabolites, Fanconi type, Glucose Monohydrate, GSD type XI, TAF230, BrdU, gluco-hexose, GLUT2 deficiency, d230, criteria, Glucose, Streptomycin Grünenthal, 5-bromo-2'-deoxy-, L Isomer, secondary metabolites, dTAFII250, high weight, FBS, Fbs, Strepto Fatol, guidelines, protein-containing complex, EfW1, TYPE, Arnold-Chiari malformation type 2, L-(+)-arginine, Ly113, DAGA4, osteoblastic sarcoma cell line, mg/L, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, polypeptide chain, dmTAF1, Strepto-Fatol, Taf230, heavy, Strepto Hefa, Fanconi Bickel syndrome, light, Lysine, CG4443, MAM, SCG3, Metabolic Profile, pseudo-phlorizin diabetes, TAF250, Taf200, Urd, dTAF[[II]]250, D-Streptamine, cell, Metabolomes, Lichtquant, Profile, hepatic glycogenosis with Fanconi nephropathy, Taf1p, Visible, 3H)-dione, dTAF250, Allo Uridine, Estreptomicina CEPA, glycogen storage disease type 11, GLMR, K3K7.20, photon, L-Arg, Antibiotics, Broxuridine, TR2, Chiari malformation type 2, Arnold Chiari malformation type II, TAF, 5 Bromodeoxyuridine, Anhydrous, K3K7_20, 5-Bromodeoxyuridine, D-MEM, col, DmelCG4443, TAF[[II]]250, Ubc7, (beta-D)-Isomer, 2-oxopropanoate, protein complex, Fanconi-Bickel disease, Cell Lines, l(3)84Ab, ion(1-), BG:DS00004.13, L-Isomer, CD258, DL Arginine Acetate, Cell, beta-Uridine, LGMD2C, dTAF230, Isotope, native protein, natural protein, L-Isomer Arginine, Acetate, p230, glycogen storage disease XI, Protein, Hydrochloride, TAF[[II]]250/230, TFIID, 4(1H, L Arginine, glycogen storage disease type XI, L-Lysine, osteogenic sarcoma cell line, CRL, glycogenosis, Neomycin Palmitate, Radiations, GLM-R, Taf[[II]]250, gram per litre, hepatorenal glycogenosis with renal Fanconi syndrome, 143B, TAF[[II]]230, Bromouracil Deoxyriboside, GSD type 11, DMDA1, Metabolic, Streptomycin Sulfate (2:3) Salt, HVEM-L, Chiari malformation type II, (2S)-2-amino-5-guanidinopentanoic acid, uridine, Photoradiation, metabolite, TAF[II]250, FBS1, Fbs1, Allouridine, sample population, Anhydrous Dextrose, LTg, hGLM-R, DmelCG17603, Fradiomycin Sulfate, Photoradiations, hepatorenal glycogenosis with renal fanconi syndrome, Estreptomicina Clariana, SCARMD2, 6-diaminohexanoic acid, Enisyl, TAF1, Glc"],"description_synonyms":["liquid chromatography tandem mass spectroscopy, thymus-derived chemotactic agent 4, d230, biological signaling, posttranslational modification, Lattices, small-inducible cytokine A21, Microtrabecular, SLC, Cytoplasmic Filaments, Metabolisms, Aminosaeure, GM05887, number, Aminocarbonsaeure, Amino acid, Bioenergetics, dTAFII250, Profiles, alpha-amino acid, mitochondrial signalling pathway, Ximpact, EfW1, presence, Downregulation, phosphorylation, LC-MS-MS, dmTAF[[II]]230, Filament, Cytoskeletons, dmTAF1, Taf230, Metabolism, LC-MSMS, Cytoskeletal Filaments, Line, citric acid cycle, Expenditure, Metabolic Profile, Microtrabecular Lattice, Metabolic Profiles, TAF250, study, Taf200, posttranslational amino acid modification, Ubiquitylation, dTAF[[II]]250, LCMSMS, amino acids, mitochondrial genome, TFIID TAF250, MRM, Cytoplasmic Filament, cel, Metabolomes, cell, Cytoskeletal, Profile, absent from organism, uniform, secondary lymphoid-tissue chemokine, Energy, Taf1p, labeling, posttranslational protein modification, Expenditures, Cytoplasmic, Ccl21c, dTAF250, mitochondrial signaling pathway, HOS-143b, Microtrabecular Lattices, beta chemokine exodus-2, signaling process, Ccl21b, GM05887A, ubiquitination, TAF, single organism signaling, retrograde response, LC-MS2, constant, dTAF[[II]]230, TAF[[II]]250, RCB2862., Mitochondrial DNA, Krebs cycle, Aminokarbonsaeure, LC-MS/MS, Cell Lines, Phosphorylations, TAF200, total expressed protein, l(3)84Ab, small-inducible cytokine A21c, small-inducible cytokine A21b, BG:DS00004.13, alpha-amino acids, small-inducible cytokine A21a, TAFII-250, TAF250/230, Cell, impact-a, alpha-amino carboxylic acids, Down Regulation, dTAF230, Multiple Reaction Monitoring, count in organism, TAFII250, LC/MS/MS, Down-Regulation, Receptor Down-Regulation, p230, Down-Regulation (Physiology), Cytoskeletal Filament, TAF[[II]]250/230, TFIID, activation, Lines, Energy Expenditure, Taf[[II]]250, mitochondria-nucleus signal transduction, Amino Acid, Acid, 143B, mtDNA, absence, TAF[[II]]230, PTM, Amino acids, Metabolic, SRM, Energy Expenditures, Filaments, TAF[II]250, Amino, CG17603, TAF[[II]], post-translational amino acid modification, Bioenergetic, signalling, Scya21b, CCL21, Energy Metabolisms, TCA4, mitochondrial DNA, DmelCG17603, TCA cycle, Scya21c, signalling process, Taf250, 6Ckine, post-translational modification, SR3-5, liquid chromatography-tandem mass spectroscopy, SCYA21, Lattice, liquid chromatography tandem mass spectrometry, Acids, Receptor, quantitative, UNQ784/PRO1600, E430016J11Rik, Proteomes, RWDD5, TAF230, TAF1, presence or absence in organism"],"citation_count":["0"],"additional_accession":[]},"is_claimable":true,"name":"An impaired respiratory electron chain triggers down-regulation of the energy metabolism and de-ubiquitination of solute carrier amino acid transporters","description":"We integrated metabolome and proteome profiles of the parental cell line 143B.TK- versus ρ0, including PTM analyses such as phosphorylation and ubiquitination to characterize the impact of the absence of mtDNA for the entire cell. For quantitative proteome profiling, we used a shotgun LC-MS/MS approach including the classical SILAC labeling. For comprehensive metabolome profiling, we applied a targeted LC-MS approach, based on multiple reaction monitoring (MRM).Our study revealed that mtDNA depletion leads to a non-uniform down-regulation of the mitochondrial energy metabolism in ρ0 cells on the proteome level. Metabolites of the TCA cycle were highly dysregulated which in turn had an impact on the amino acid levels, which were up regulated. Perturbation of the mitochondrial energy metabolism could lead to an activation of the retrograde response, indicated by sets of up-regulated signaling pathways in ρ0 cells, further supported by altered phosphorylation in signaling pathways and the cytoskeleton as well as de-ubiquitination of SLC transporters.","dates":{"publication":"2016-02-08","submission":"2016-01-11"},"accession":"PXD002425","cross_references":{"TAXONOMY":["44544","10090","64152","4054","9986","3880","43330","38783","83906","327160","884019","9615","2758385","7574","8782","7215","1351","75058","985076","55571","480","46835","2","1589","10306","3641","3885","6239","803","100226","1902","6915","645463","746360","135588","1134506","146479","6928","145943","NCBITaxon:6157","9778","1182590","4081","632957","380394","272563","145953","61235","178616","7227","243230","7469","92867","1123869","NCBITaxon:2","4530","6279","129249","703612","5180","1424507","284812","3555","1274432","426428","150475","10299","990346","9417","6945","347515","415540","59729","36329","9796","6287","157546","4784","2242","95486","208964","317447","575584","6282","287","230741","1148","1736231","4896","935293","725","1264690","39946","727","360106","216595","544404","260710","1283","1280","33952","3218","1843183","NCBITaxon:6191","5755","4787","931281","1836","5759","307972","190802","1432138","242619","1692259","106592","2261","1117957","260704","6183","260705","260707","885318","7029","4558","626528","1736309","43179","698936","160488","209285","5664","67825","1249668","6192","1263854","35554","32046","NCBITaxon:10359","NCBITaxon:1313","4565","860688","607699","7955","7959","70448","300641","8022","235443","6763","1076","224308","185431","169963","28104","2157","4577","1216979","4232","135622","334747","2697049","8030","10239","29760","10117","3818","58334","9913","1274414","1639","10116","5691","5693","13076","74940","98334","408172","128161","2042546","876138","3708","1274423","990119","1274420","1274426","9925","8839","3702","1000589","9940","34305","554","28532","1895","1773","1193501","8726","317","1450511","8723","8724","8727","95648","188229","5476","7091","115104","58002","3055","1480154","180066","9031","3847","562","3603","1423","85962","9825","101510","9823","1174673","4932","11676","2759","67767","373153","44685","NCBITaxon:9615","29722","1097677","573","493760","83334","1911079","2762","80863","6326","6689","83332","10312","9838","237561","241368","749200","360094","3197","196627","9606","157295","171101","51515","256737"],"pubmed":["26852163"]}}