Malonate induces the assembly of cytoplasmic stress granules

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 (m) and ATP level. The phosphorylation levels of eIF2 and 4EBP1 protein were affected upon mitochondrial dysfunction. However, knockdown of 4EBP1 affected SG formation, rather than eIF2. 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，一种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）是应激过程中的一种动态焦点结构。关于线粒体应激与应激颗粒组装之间联系的研究仍然有限。在此，我们证明了丙二酸处理除了导致线粒体应激（包括活性氧形成增加、线粒体膜电位（m）和ATP水平降低）之外，还会导致应激颗粒形成和翻译抑制。在线粒体功能障碍时，eIF2和4EBP1蛋白的磷酸化水平受到影响。然而，敲低4EBP1会影响应激颗粒形成，而敲低eIF2则不会。此外，在线粒体应激下ATP水平的升高增强了丙二酸诱导的应激颗粒聚集。总体而言，丙二酸刺激触发线粒体应激，并通过4EBP1途径诱导非经典细胞应激颗粒的组装。