Fu Xue, Gao Xingjie, Ge Lin, Cui Xiaoteng, Su Chao, Yang Wendong, Sun Xiaoming, Zhang Wei, Yao Zhi, Yang Xi, Yang Jie
Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.
Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.
FEBS Lett. 2016 Jan;590(1):22-33. doi: 10.1002/1873-3468.12049. Epub 2016 Jan 8.
Malonate, a classic inhibitor of respiratory electron transport chain, induces mitochondrial stress. Stress granules (SGs) are a kind of dynamic foci structure during stress. The study on the connection of mitochondrial stress and SG assembly is still limited. Here, we demonstrated that malonate treatment leads to SG formation and translation inhibition, apart from mitochondrial stress, including enhanced ROS formation, reduced mitochondrial Δψm and ATP level. The phosphorylation levels of eIF2α and 4EBP1 protein were affected upon mitochondrial dysfunction. However, knockdown of 4EBP1 affected SG formation, rather than eIF2α. In addition, an increase of ATP level under mitochondrial stress enhanced malonate-induced SG aggregation. Overall, malonate stimulation triggers mitochondrial stress and induces the assembly of non-canonical cellular SGs via 4EBP1 pathway.
丙二酸是呼吸电子传递链的经典抑制剂，可诱导线粒体应激。应激颗粒（SGs）是应激期间一种动态的病灶结构。关于线粒体应激与SG组装之间联系的研究仍然有限。在这里，我们证明，丙二酸处理除了诱导线粒体应激外，还会导致SG形成和翻译抑制，包括增强ROS生成、降低线粒体Δψm和ATP水平。线粒体功能障碍时，eIF2α和4EBP1蛋白的磷酸化水平会受到影响。然而，敲低4EBP1会影响SG形成，而不是eIF2α。此外，线粒体应激下ATP水平的升高增强了丙二酸诱导的SG聚集。总体而言，丙二酸刺激触发线粒体应激，并通过4EBP1途径诱导非典型细胞SG的组装。
