Comparison of proteomic and metabolomic profiles of mutants of the mitochondrial respiratory chain in Caenorhabditis elegans

P G Morgan; R Higdon; N Kolker; A T Bauman; O Ilkayeva; C B Newgard; E Kolker; L M Steele; M M Sedensky

doi:10.1016/j.mito.2014.12.004

Comparison of proteomic and metabolomic profiles of mutants of the mitochondrial respiratory chain in Caenorhabditis elegans

Mitochondrion. 2015 Jan:20:95-102. doi: 10.1016/j.mito.2014.12.004. Epub 2014 Dec 19.

Authors

P G Morgan¹, R Higdon², N Kolker³, A T Bauman⁴, O Ilkayeva⁵, C B Newgard⁵, E Kolker⁶, L M Steele⁷, M M Sedensky⁸

Affiliations

¹ 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.
² 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.
³ High-throughput Analysis Core, Seattle Children's Research Institute, USA; Data-Enabled Life Sciences Alliance (DELSA Global), USA.
⁴ Bioinformatics and High-throughput Analysis Laboratory, USA.
⁵ 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.
⁶ 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.
⁷ Center for Developmental Therapeutics, Seattle Children's Research Institute, USA.
⁸ Department of Anesthesiology and Pain Medicine, University of Washington, USA; Center for Developmental Therapeutics, Seattle Children's Research Institute, USA.

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.

Keywords: C. elegans; Gene expression; Genetics; Metabolomics; Mitochondria; Proteomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Caenorhabditis elegans / chemistry*
Caenorhabditis elegans Proteins / analysis
Caenorhabditis elegans Proteins / genetics
Electron Transport Chain Complex Proteins / genetics*
Metabolome*
Mitochondria / enzymology*
Mitochondrial Proteins / genetics
Mutation*
Proteome / analysis*

Substances

Caenorhabditis elegans Proteins
Electron Transport Chain Complex Proteins
Mitochondrial Proteins
Proteome

Abstract

Publication types

MeSH terms

Substances

Grants and funding