Back to Search
Start Over
LC-MS proteomics analysis of the insulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism.
- Source :
-
Journal of proteome research [J Proteome Res] 2014 Apr 04; Vol. 13 (4), pp. 1938-56. Date of Electronic Publication: 2014 Mar 03. - Publication Year :
- 2014
-
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 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.
- Subjects :
- Animals
Caenorhabditis elegans metabolism
Caenorhabditis elegans Proteins analysis
Caenorhabditis elegans Proteins chemistry
Caenorhabditis elegans Proteins metabolism
Forkhead Transcription Factors
Gene Knockdown Techniques
Metabolic Networks and Pathways genetics
Mutation genetics
Proteome analysis
Proteome chemistry
Proteome metabolism
Proteomics methods
Transcription Factors analysis
Transcription Factors chemistry
Transcription Factors genetics
Transcription Factors metabolism
Caenorhabditis elegans genetics
Caenorhabditis elegans physiology
Caenorhabditis elegans Proteins genetics
Insulin genetics
Insulin-Like Growth Factor I genetics
Proteome genetics
Receptor, Insulin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 13
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 24555535
- Full Text :
- https://doi.org/10.1021/pr401081b