Mitochondrial reactive oxygen species (ROS) function intrinsically within cells to induce cell damage, regulate transcription, and cause genome instability. However, we know little about how mitochondrial ROS production non-cell autonomously impacts cell-cell signaling. Here, we show that mitochondrial dysfunction inhibits the plasma membrane localization of cell surface receptors that drive cell-cell communication during oogenesis. Within minutes, we found that mitochondrial ROS impairs exocyst membrane binding and leads to defective endosomal recycling. This endosomal defect impairs the trafficking of receptors, such as the Notch ligand Delta, during oogenesis. Remarkably, we found that overexpressing RAB11 restores ligand trafficking and rescues the developmental defects caused by ROS production. ROS production from adjacent cells acutely initiates a transcriptional response associated with growth and migration by suppressing Notch signaling and inducing extra cellualr matrix (ECM) remodeling. Our work reveals a conserved rapid response to ROS production that links mitochondrial dysfunction to the non-cell autonomous regulation of cell-cell signaling.

中文翻译：

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线粒体 ROS 对细胞间信号传导和分化的非细胞自主调节。


线粒体活性氧 （ROS） 在细胞内起着内在的作用，以诱导细胞损伤、调节转录并导致基因组不稳定。然而，我们对线粒体 ROS 产生非细胞自主如何影响细胞间信号传导知之甚少。在这里，我们表明线粒体功能障碍抑制了细胞表面受体的质膜定位，这些受体在卵子发生过程中驱动细胞间通讯。几分钟内，我们发现线粒体 ROS 损害了外囊膜结合并导致内体回收缺陷。这种内体缺陷会损害卵子发生过程中受体的运输，例如 Notch 配体 Delta。值得注意的是，我们发现过表达 RAB11 可恢复配体运输并挽救 ROS 产生引起的发育缺陷。相邻细胞产生的 ROS 通过抑制 Notch 信号传导和诱导细胞外基质 （ECM） 重塑，急性启动与生长和迁移相关的转录反应。我们的工作揭示了对 ROS 产生的保守快速反应，该反应将线粒体功能障碍与细胞间信号的非细胞自主调节联系起来。