title: Interactions among mitochondrial proteins altered in glioblastoma.
abstract: Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥ 2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein-protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology.
authors.affiliation: Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, Edinburgh, EH8 9XD, UK. ruth.deighton@ed.ac.uk.
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Deighton
authors.affiliation: SynthSys, Synthetic and Systems Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Bihan
authors.affiliation: SynthSys, Synthetic and Systems Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Martin
authors.affiliation: Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, UK.
authors.forename: Alice M J
authors.initials: AMJ
authors.lastname: Gerth
authors.affiliation: Applied Neurobiology Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Mailis
authors.initials: M
authors.lastname: McCulloch
authors.affiliation: Applied Neurobiology Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Edgar
authors.affiliation: SynthSys, Synthetic and Systems Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Lorraine E
authors.initials: LE
authors.lastname: Kerr
authors.affiliation: Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Whittle
authors.affiliation: Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, UK.
authors.forename: James
authors.initials: J
authors.lastname: McCulloch
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism / Q000601:surgery / Q000648:ultrastructure; D001932:Brain Neoplasms / Q000378:metabolism* / Q000601:surgery / Q000648:ultrastructure; D015331:Cohort Studies; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000601:surgery / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism*; D040901:Proteomics; D055815:Young Adult
chemical_list: D024101:Mitochondrial Proteins
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