Proteomic and metabolomic analyses of mitochondrial complex I-deficient mouse model generated by spontaneous B2 short interspersed nuclear element (SINE) insertion into NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) gene

DW Leong; JC Komen; CA Hewitt; E Arnaud; M McKenzie; B Phipson; M Bahlo; A Laskowski; SA Kinkel; GM Davey; WR Heath; AK Voss; RP Zahedi; JJ Pitt; R Chrast; A Sickmann; MT Ryan; GK Smyth; DR Thorburn; HS Scott

Journal article

Proteomic and metabolomic analyses of mitochondrial complex I-deficient mouse model generated by spontaneous B2 short interspersed nuclear element (SINE) insertion into NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) gene

DW Leong, JC Komen, CA Hewitt, E Arnaud, M McKenzie, B Phipson, M Bahlo, A Laskowski, SA Kinkel, GM Davey, WR Heath, AK Voss, RP Zahedi, JJ Pitt, R Chrast, A Sickmann, MT Ryan, GK Smyth, DR Thorburn, HS Scott

Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2012

DOI: 10.1074/jbc.M111.327601

Abstract

Eukaryotic cells generate energy in the form of ATP, through a network of mitochondrial complexes and electron carriers known as the oxidative phosphorylation system. In mammals, mitochondrial complex I (CI) is the largest component of this system, comprising 45 different subunits encoded by mitochondrial and nuclear DNA. Humans diagnosed with mutations in the gene NDUFS4, encoding a nuclear DNA-encoded subunit of CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, a neurodegenerative disease with onset in infancy or early childhood. Mitochondria from NDUFS4 patients usually lack detectable NDUFS4 protein and show a CI stability/assembly defect. Here, we ..

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University of Melbourne Researchers

Belinda Phipson Author

Melanie Bahlo Author

Gayle Davey Author

William Heath Author

Grants

Awarded by National Health and Medical Research Council(NHMRC)

Funding Acknowledgements

This work was supported by an Australian Postgraduate Award (to S.A.K.), National Health and Medical Research Council(NHMRC) fellowships (to H.H.S, D.R.T., G.K.S., and A.K.V.), NHMRC career development awards (to M.M. and M.B.), NHMRC Program Grant 257501, and NHMRC Project Grants 607403 and 602530, the Australian Research Council (to M.T.R.), the Victorian Government's Operational Infrastructure Support Program, and the Nossal Leadership Award from the Walter and Eliza Hall Institute of Medical Research (to H.S.S.). Efficient animal management and data collection were facilitated by the Walter and Eliza Hall Institute of Medical Research (WEHI) and Murdoch Childrens Research Institute animal technicians. Processing of histological samples was aided by WEHI Histology and the Integrative Neuroscience Facility. Affymetrix exon arrays and linkage genotyping were performed by the Australian Genome Research Facility, which was established through the Commonwealth-funded Major National Research Facilities Program.