PDF(Pubmed)
Abstract：
The metabolism of glioma cells exhibits significant heterogeneity and is partially responsible for treatment outcomes. Given this variability, we hypothesized that the effectiveness of treatments targeting various metabolic pathways depends on the bioenergetic profiles and mitochondrial status of glioma cells. To this end, we analyzed mitochondrial biomass, mitochondrial protein density, oxidative phosphorylation (OXPHOS), and glycolysis in a panel of eight glioma cell lines. Our findings revealed considerable variability: mitochondrial biomass varied by up to 3.2-fold, the density of mitochondrial proteins by up to 2.1-fold, and OXPHOS levels by up to 7.3-fold across the cell lines. Subsequently, we stratified glioma cell lines based on their mitochondrial status, OXPHOS, and bioenergetic fitness. Following this stratification, we utilized 16 compounds targeting key bioenergetic, mitochondrial, and related pathways to analyze the associations between induced changes in cell numbers, proliferation, and apoptosis with respect to their steady-state mitochondrial and bioenergetic metrics. Remarkably, a significant fraction of the treatments showed strong correlations with mitochondrial biomass and the density of mitochondrial proteins, suggesting that mitochondrial status may reflect glioma cell sensitivity to specific treatments. Overall, our results indicate that mitochondrial status and bioenergetics are linked to the efficacy of treatments targeting metabolic pathways in glioma.
摘要：
神经胶质瘤细胞的代谢表现出明显的异质性，并部分负责治疗结果。鉴于这种可变性，我们假设靶向各种代谢途径的治疗的有效性取决于神经胶质瘤细胞的生物能量谱和线粒体状态.为此,我们分析了线粒体生物量，线粒体蛋白质密度，氧化磷酸化（OXPHOS），和一组八种神经胶质瘤细胞系的糖酵解。我们的发现揭示了相当大的变异性：线粒体生物量变化高达3.2倍，线粒体蛋白质的密度高达2.1倍，和OXPHOS水平在整个细胞系中高达7.3倍。随后，我们根据神经胶质瘤细胞系的线粒体状态对它们进行分层，OXPHOS,和生物活力健身。在这种分层之后，我们利用了16种靶向关键生物能量的化合物，线粒体，和相关的途径来分析诱导的细胞数量变化之间的关联，扩散,和凋亡相对于其稳态线粒体和生物能量指标。值得注意的是,显著部分的处理显示与线粒体生物量和线粒体蛋白的密度有很强的相关性,提示线粒体状态可能反映神经胶质瘤细胞对特定治疗的敏感性。总的来说,我们的结果表明,线粒体状态和生物能学与神经胶质瘤靶向代谢途径治疗的疗效相关.
