Deighton Ruth F, Le Bihan Thierry, Martin Sarah F, Gerth Alice M J, McCulloch Mailis, Edgar Julia M, Kerr Lorraine E, Whittle Ian R, McCulloch James
Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, Edinburgh, EH8 9XD, UK.
SynthSys, Synthetic and Systems Biology, University of Edinburgh, Edinburgh, UK.
J Neurooncol. 2014 Jun;118(2):247-256. doi: 10.1007/s11060-014-1430-5. Epub 2014 Apr 13.
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.
线粒体功能障碍被认为是胶质母细胞瘤（GBM）病理生理学的核心，但尚未对GBM中与线粒体功能不可或缺的蛋白质进行系统分析。通过无标记液相色谱质谱法确定了GBM患者线粒体富集组分中蛋白质的变化。在线粒体富集组分中鉴定出256种与线粒体相关的蛋白质，其中117种线粒体蛋白质在GBM中显著（倍数变化≥2）且有明显改变（p≤0.05）。与氧化损伤相关的蛋白质（包括过氧化氢酶、超氧化物歧化酶2、过氧化物酶1和过氧化物酶4）在GBM中增加。蛋白质-蛋白质相互作用分析突出显示与能量代谢相关的多种蛋白质减少（特别是呼吸链蛋白质，包括23种复合体I蛋白质）。GBM的电子显微镜定性超微结构分析显示，GBM中线粒体嵴溶解的发生率明显更高。这项研究突出了GBM病理生理学中发生的复杂线粒体蛋白质组学调整。
