title: Comparison of proteomic and metabolomic profiles of mutants of the mitochondrial respiratory chain in Caenorhabditis elegans.
abstract: Single-gene mutations that disrupt mitochondrial respiratory chain function in Caenorhabditis elegans change patterns of protein expression and metabolites. Our goal was to develop useful molecular fingerprints employing adaptable techniques to recognize mitochondrial defects in the electron transport chain. We analyzed mutations affecting complex I, complex II, or ubiquinone synthesis and discovered overarching patterns in the response of C. elegans to mitochondrial dysfunction across all of the mutations studied. These patterns are in KEGG pathways conserved from C. elegans to mammals, verifying that the nematode can serve as a model for mammalian disease. In addition, specific differences exist between mutants that may be useful in diagnosing specific mitochondrial diseases in patients.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Washington, USA; Center for Developmental Therapeutics, Seattle Children's Research Institute, USA. Electronic address: pgm4@uw.edu.
authors.forename: P G
authors.initials: PG
authors.lastname: Morgan
authors.affiliation: Bioinformatics and High-throughput Analysis Laboratory, USA; High-throughput Analysis Core, Seattle Children's Research Institute, USA; Data-Enabled Life Sciences Alliance (DELSA Global), USA.
authors.forename: R
authors.initials: R
authors.lastname: Higdon
authors.affiliation: High-throughput Analysis Core, Seattle Children's Research Institute, USA; Data-Enabled Life Sciences Alliance (DELSA Global), USA.
authors.forename: N
authors.initials: N
authors.lastname: Kolker
authors.affiliation: Bioinformatics and High-throughput Analysis Laboratory, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Bauman
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA; Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: O
authors.initials: O
authors.lastname: Ilkayeva
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA; Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Bioinformatics and High-throughput Analysis Laboratory, USA; High-throughput Analysis Core, Seattle Children's Research Institute, USA; Data-Enabled Life Sciences Alliance (DELSA Global), USA; Department of Biomedical Informatics & Medical Education, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Department of Chemistry and Chemical Biology, College of Science, Northeastern University, Boston, MA 02115, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kolker
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Steele
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Washington, USA; Center for Developmental Therapeutics, Seattle Children's Research Institute, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Sedensky
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics*; D055442:Metabolome; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D020543:Proteome / Q000032:analysis*
chemical_list: D029742:Caenorhabditis elegans Proteins; D045222:Electron Transport Chain Complex Proteins; D024101:Mitochondrial Proteins; D020543:Proteome
keywords: C. elegans; Gene expression; Genetics; Metabolomics; Mitochondria; Proteomics