Interactions among mitochondrial proteins altered in glioblastoma

作者：Ruth F. Deighton, Thierry Le Bihan, Sarah F. Martin, A. Gerth, Mailis C. McCulloch, Julia M. Edgar, Lorraine E. Kerr, Ian R. Whittle, James McCulloch · 发表于：Journal of Neuro-Oncology · 年份：2014 · DOI：10.1007/s11060-014-1430-5 · 被引用次数：77 · 研究领域：Mitochondrial Function and Pathology、Glioma Diagnosis and Treatment、Cancer, Hypoxia, and Metabolism

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.