Advanced search
1 file | 5.95 MB Add to list

LC-MS proteomics analysis of the iInsulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism

(2014) JOURNAL OF PROTEOME RESEARCH. 13(4). p.1938-1956
Author
Organization
Abstract
The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. 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 beta-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.
Keywords
gene expression, Caenorhabditis elegans, mass spectrometry, metabolism, physiology, aging, NEMATODE CAENORHABDITIS-ELEGANS, METHYLMALONYL-COA EPIMERASE, PYRUVATE-KINASE ACTIVITY, LIVED DAF-2 MUTANTS, ATP-CITRATE LYASE, LARGE GENE LISTS, C-ELEGANS, LIFE-SPAN, DAUER LARVA, INSULIN-RESISTANCE

Downloads

  • Depuydt-JPR 2014 v13p1938.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 5.95 MB

Citation

Please use this url to cite or link to this publication:

MLA
Depuydt, Geert, et al. “LC-MS Proteomics Analysis of the IInsulin/IGF-1-Deficient Caenorhabditis Elegans Daf-2(E1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism.” JOURNAL OF PROTEOME RESEARCH, vol. 13, no. 4, 2014, pp. 1938–56, doi:10.1021/pr401081b.
APA
Depuydt, G., Xie, F., Petyuk, V. A., Smolders, A., Brewer, H. M., Camp, D. G., II, … Braeckman, B. (2014). LC-MS proteomics analysis of the iInsulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism. JOURNAL OF PROTEOME RESEARCH, 13(4), 1938–1956. https://doi.org/10.1021/pr401081b
Chicago author-date
Depuydt, Geert, Fang Xie, Vladislav A Petyuk, Arne Smolders, Heather M Brewer, David G Camp II, Richard D Smith, and Bart Braeckman. 2014. “LC-MS Proteomics Analysis of the IInsulin/IGF-1-Deficient Caenorhabditis Elegans Daf-2(E1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism.” JOURNAL OF PROTEOME RESEARCH 13 (4): 1938–56. https://doi.org/10.1021/pr401081b.
Chicago author-date (all authors)
Depuydt, Geert, Fang Xie, Vladislav A Petyuk, Arne Smolders, Heather M Brewer, David G Camp II, Richard D Smith, and Bart Braeckman. 2014. “LC-MS Proteomics Analysis of the IInsulin/IGF-1-Deficient Caenorhabditis Elegans Daf-2(E1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism.” JOURNAL OF PROTEOME RESEARCH 13 (4): 1938–1956. doi:10.1021/pr401081b.
Vancouver
1.
Depuydt G, Xie F, Petyuk VA, Smolders A, Brewer HM, Camp DG II, et al. LC-MS proteomics analysis of the iInsulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism. JOURNAL OF PROTEOME RESEARCH. 2014;13(4):1938–56.
IEEE
[1]
G. Depuydt et al., “LC-MS proteomics analysis of the iInsulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism,” JOURNAL OF PROTEOME RESEARCH, vol. 13, no. 4, pp. 1938–1956, 2014.
@article{4417305,
  abstract     = {{The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. 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 beta-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.}},
  author       = {{Depuydt, Geert and Xie, Fang and Petyuk, Vladislav A and Smolders, Arne and Brewer, Heather M and Camp, David G, II and Smith, Richard D and Braeckman, Bart}},
  issn         = {{1535-3893}},
  journal      = {{JOURNAL OF PROTEOME RESEARCH}},
  keywords     = {{gene expression,Caenorhabditis elegans,mass spectrometry,metabolism,physiology,aging,NEMATODE CAENORHABDITIS-ELEGANS,METHYLMALONYL-COA EPIMERASE,PYRUVATE-KINASE ACTIVITY,LIVED DAF-2 MUTANTS,ATP-CITRATE LYASE,LARGE GENE LISTS,C-ELEGANS,LIFE-SPAN,DAUER LARVA,INSULIN-RESISTANCE}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1938--1956}},
  title        = {{LC-MS proteomics analysis of the iInsulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism}},
  url          = {{http://dx.doi.org/10.1021/pr401081b}},
  volume       = {{13}},
  year         = {{2014}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: