Dept. of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Dept. of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Neurosci Lett. 2019 Sep 25;710:132931. doi: 10.1016/j.neulet.2017.06.050. Epub 2017 Jun 28.
Experimental evidence supports an intricate association between inflammation and mitochondrial dysfunction as main contributors of neurological diseases. Inflammatory mediators produced by activated microglia and infiltrated immune cells trigger intracellular signalling cascades that can alter cellular mitochondrial metabolism. Cytokines, particularly tumor necrosis factor-alpha, impede mitochondrial oxidative phosphorylation and associated ATP production and instigate mitochondrial reactive oxygen species production. This culminates in mitochondrial membrane permeabilization, altered mitochondrial dynamics and might ultimately result in cell death. When severely injured mitochondria are not appropriately removed by mitophagy they can release their contents into the cytosol and extracellular environment and thereby amplify the inflammatory process. Here we provide a comprehensive overview on how inflammatory mediators impair mitochondrial metabolism and discuss how defective mitochondria can elicit and potentiate an inflammatory response.
实验证据支持炎症和线粒体功能障碍之间的复杂关联，它们是神经疾病的主要诱因。激活的小胶质细胞和浸润的免疫细胞产生的炎症介质触发细胞内信号级联反应，从而改变细胞线粒体代谢。细胞因子，特别是肿瘤坏死因子-α，会抑制线粒体氧化磷酸化以及相关的 ATP 生成，并引发线粒体活性氧物质的生成。这最终导致线粒体膜通透性改变、线粒体动力学改变，并可能导致细胞死亡。当受损的线粒体不能被自噬有效地清除时，它们会将内容物释放到细胞质和细胞外环境中，从而放大炎症反应。在这里，我们全面概述了炎症介质如何损害线粒体代谢，并讨论了有缺陷的线粒体如何引发和增强炎症反应。
