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In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC-MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity."],"pubmed_title":["LC-MS proteomics analysis of the insulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism."],"pubmed_authors":["Depuydt Geert G,Xie Fang F,Petyuk Vladislav A VA,Smolders Arne A,Brewer Heather M HM,Camp David G DG 2nd,Smith Richard D RD,Braeckman Bart P BP,","Depuydt Geert G,Xie Fang F,Petyuk Vladislav A VA,Smolders Arne A,Brewer Heather M HM,Camp David G DG,Smith Richard D RD,Braeckman Bart P BP,","Depuydt Geert G, Xie Fang F, Petyuk Vladislav A VA, Smolders Arne A, Brewer Heather M HM, Camp David G DG, Smith Richard D RD, Braeckman Bart P BP"],"name_synonyms":["Chain, Soluble, IGF-I, Insulin B Chain, roundworm <Caenorhabditis elegans>, Nemata, metabolic energy generation, Regular, determination, elegan, INS, Igf-I, somatomedin-C, CROM, somatomedin, Insulin B, Caenorhabditis, Caenorhabditis elegan, Regular Insulin, roundworm, nematode, Iletin, Sodium Insulin, DAF, IGF1, Insulin, MGF, mechano growth factor, chemical analysis, nematodes, Insulin A Chain, roundworms, CR, TC, intermediary metabolism., C730016P09Rik, Sodium, assay, Novolin, energy pathways, cellular metabolism, Igf-1, Soluble Insulin, Rhabditis elegans"],"description_synonyms":["transcription factor, RNA polymerase II core promoter proximal region sequence-specific binding, APR, data, T-cell leukemia, metabolic energy generation, 2.1.1.-, Eu-HMTase1, GLP, LRP, nucleocapsid, number, Liquid Chromatography, CROM, APOER, Euchromatic histone-lysine N-methyltransferase 1, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, Spectrum Analyses, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, G9a-like protein 1, Transcription Factor, presence, Spectrum Analysis, KMT1D, Spectroscopy, transcription factor activity, 2.1.1.43, count in organism, CD91, zinc ion regulated core promoter proximal region sequence-specific DNA binding, GLP1, count, responsivity, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, FP13812, Mass, Histone H3-K9 methyltransferase 5, RNA polymerase II transcription factor activity, TGFBR5, Analysis, sequence-specific DNA binding, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, energy pathways, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, Mass Spectrum Analyses, activation, Mass Spectroscopy, Mass Spectrum Analysis, Mass Spectrum, reactivity, Transcription, Factors, core., Analyses, NOXA, D330003E03, Spectrometry, Lysine N-methyltransferase 1D, sequence-specific DNA binding RNA polymerase II transcription factor activity, metal ion regulated core promoter proximal region sequence-specific binding, copper ion regulated core promoter proximal region sequence-specific binding, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Transcription factor, 9230102N17Rik, CLLD7, EUHMTASE1, A2MR, DAF, mKIAA1876, RNA polymerase II proximal promoter sequence-specific DNA binding, copper ion regulated proximal promoter sequence-specific DNA binding, intermediary metabolism, LRP1A, CR, TC, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, quantitative, response, cellular metabolism, H3-K9-HMTase 5, metal ion regulated sequence-specific DNA binding, Proteomes, IGFBP3R, metal ion regulated proximal promoter sequence-specific DNA binding, CLLL7, presence or absence in organism, sequence-specific transcription regulatory region DNA binding, RNA polymerase II distal enhancer sequence-specific binding, bA188C12.1"],"pubmed_title_synonyms":["Chain, Soluble, IGF-I, Insulin B Chain, roundworm <Caenorhabditis elegans>, Nemata, metabolic energy generation, Regular, determination, elegan, INS, Igf-I, somatomedin-C, CROM, somatomedin, Insulin B, Caenorhabditis, Caenorhabditis elegan, Regular Insulin, roundworm, nematode, Iletin, Sodium Insulin, DAF, IGF1, Insulin, MGF, mechano growth factor, chemical analysis, nematodes, Insulin A Chain, roundworms, CR, TC, intermediary metabolism., C730016P09Rik, Sodium, assay, Novolin, energy pathways, cellular metabolism, Igf-1, Soluble Insulin, Rhabditis elegans"],"pubmed_abstract_synonyms":["biochemical pathways, sodium salt, Soluble, transcription factor, acido graso, glucose biosynthetic process, Insulin B Chain, T-cell leukemia, Metabolic Process, Materials, acidos grasos, Eu-HMTase1, GLP, Metabolisms, Metabolic Concepts, Embden-Meyerhof, Bioenergetics, Euchromatic histone-lysine N-methyltransferase 1, Embden Meyerhof Parnas Pathway, Ccne, responsivity, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, FP13812, Concepts, Embden-Meyerhof Pathway, Analysis, Metabolism Concept, PAST, Expenditure, Phenomenon, Nutrient, present in fewer numbers in organism, multicellular organismal biosynthetic process, Mass Spectrum Analysis, single-organism biosynthetic process, Gene Expressions, enzymes, Genomes, Analyses, catabolism, anabolism, Length of Life, somatomedin-C, hypoplasia, Pathways, metabolic process resulting in cell growth, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, roundworm, decreased, IGF1, signaling process, nematodes, intermediary metabolism, roundworms, CR, TC, 2-(14)C-labeled, biotransformation, C730016P09Rik, HPAST1, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, associated, Catabolism, CLLL7, single organism signaling, RNA polymerase II distal enhancer sequence-specific binding, bA188C12.1, incorporation, IGF-I, RNA polymerase II core promoter proximal region sequence-specific binding, Regular, Pathway, Process, Krebs cycle, one-carbon metabolism, metabolism resulting in cell growth, Igf-I, Liquid Chromatography, CROM, anaerobic glycolysis, somatomedin, Fettsaeuren, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, G9a-like protein 1, Embden-Meyerhof-Parnas, INSDC_feature:misc_RNA, Spectrum Analysis, Citric Acid, Regular Insulin, KMT1D, Spectroscopy, Embden-Meyerhof-Parnas Pathway, count, mechano growth factor, Genetic Materials, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, Tricarboxylic Acid Cycle, glyoxalic acid, Igf-1, Soluble Insulin, Genetic Material, activation, length of life, Factors, tyrosine breakdown, D330003E03, Spectrometry, Lysine N-methyltransferase 1D, whole genome, Caenorhabditis, PAST1, Krebs, Nutrients, Transcription factor, turnover, Embden-Meyerhof pathway, fatty acids, Energy Metabolisms, EUHMTASE1, glycolysis, Material, Tricarboxylic Acid, glyoxylate, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, Cistron, metal ion regulated sequence-specific DNA binding, Embden-Meyerhof Pathways, metal ion regulated proximal promoter sequence-specific DNA binding, biological signaling, H-PAST, Processes, elegan, Biocatalysts, nucleocapsid, number, Gene, Insulin B, biosynthesis, Tricarboxylic Acid Cycles, Spectrum Analyses, Metabolic Processes, Transcription Factor, presence, CYCLE, zinc ion regulated core promoter proximal region sequence-specific DNA binding, reduced, acides gras, subnumerary, Length of Life., Metabolism, 14C-labeled, Insulin, Krebs Cycle, resistance, Cycle, Mass, citric acid cycle, tiny, sequence-specific DNA binding, energy pathways, Metabolism Phenomena, Mass Spectroscopy, Chain, Cycles, study, reactivity, Transcription, one-carbon transfer metabolic process, Genetic, formation, nutrients, Metabolic Concept, Energy, decreased number, Expenditures, Caenorhabditis elegan, Expressions, synthesis, nematode, Iletin, CLLD7, DAF, RNA polymerase II proximal promoter sequence-specific DNA binding, OC([*])=O, copper ion regulated proximal promoter sequence-specific DNA binding, Expression, H3-K9-HMTase 5, modifed Embden-Meyerhof pathway, Citric Acid Cycles, small, nutrient, roundworm <Caenorhabditis elegans>, Nemata, metabolic energy generation, use, Embden Meyerhof Pathway, 2.1.1.-, degradation, tyrosine catabolism, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, enzyme activity, Factor, Cistrons, Concept, Metabolic Phenomena, transcription factor activity, Metabolism Concepts, 2.1.1.43, 14C2-labeled, Fettsaeure, count in organism, glyoxylic acid, GLP1, Sodium Insulin, one carbon metabolic process, Insulin A Chain, Phenomena, Histone H3-K9 methyltransferase 5, one carbon metabolism, RNA polymerase II transcription factor activity, core, Sodium, Novolin, CHO2R, metabolism, Rhabditis elegans, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, Foods, Mass Spectrum Analyses, Metabolic Phenomenon, Energy Expenditure, Mass Spectrum, mobilization, multicellular organism metabolic process, biodegradation, Metabolic, underdeveloped, tyrosine degradation, INS, Energy Expenditures, glucose biosynthesis, acide gras, sequence-specific DNA binding RNA polymerase II transcription factor activity, metal ion regulated core promoter proximal region sequence-specific binding, copper ion regulated core promoter proximal region sequence-specific binding, Embden-Meyerhof-Parnas pathway, signalling, 9230102N17Rik, Bioenergetic, single-organism metabolic process, TCA cycle, signalling process, mKIAA1876, MGF, one-carbon transfer metabolism, calcium salt, regulation, response, quantitative, cellular metabolism, Anabolism, presence or absence in organism, sequence-specific transcription regulatory region DNA 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File: c_elegans_A_3_8_21Apr10_Draco_10-03-04.mzml. Published as part of J Proteome Res. 2014 Apr 4;13(4):1938-56  . From the Abstract: {{i}} ... Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC-MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways ... {{/i}}","dates":{"submission":"2015-05-15"},"accession":"GPM32310019900","cross_references":{"pubmed":["24555535"],"Pride":["PXD002161"],"pride":[],"Pride Archive":["PXD002161"]}}