Graier Wolfgang F, Malli Roland, Kostner Gerhard M
Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Graz, Austria.
Trends Endocrinol Metab. 2009 May;20(4):186-93. doi: 10.1016/j.tem.2009.01.004. Epub 2009 Apr 7.
Lipotoxicity occurs as a consequence of chronic exposure of non-adipose tissue and cells to elevated concentrations of fatty acids, triglycerides and/or cholesterol. The contribution of mitochondria to lipotoxic cell dysfunction, damage and death is associated with elevated production of reactive oxygen species and initiation of apoptosis. Although there is a broad consensus on the involvement of these phenomena with lipotoxicity, the molecular mechanisms that initiate, mediate and trigger mitochondrial dysfunction in response to substrate overload remain unclear. Here, we focus on protein phosphorylation as an important phenomenon in lipotoxicity that harms mitochondria-related signal transduction and integration in cellular metabolism. Moreover, the degradation of mitochondria by mitophagy is discussed as an important landmark that leads to cellular apoptosis in lipotoxicity.
脂毒性是由于非脂肪组织和细胞长期暴露于高浓度脂肪酸、甘油三酯和/或胆固醇而产生的。线粒体对脂毒性细胞功能障碍、损伤和死亡的作用与活性氧的产生增加和细胞凋亡的启动有关。尽管人们普遍认为这些现象与脂毒性有关，但响应底物过载引发、介导和触发线粒体功能障碍的分子机制仍不清楚。在这里，我们关注蛋白质磷酸化，它是脂毒性中的一个重要现象，会损害细胞代谢中与线粒体相关的信号转导和整合。此外，线粒体自噬对线粒体的降解被认为是脂毒性中导致细胞凋亡的一个重要标志。
