Northwestern University Feinberg School of Medicine, Department of Pediatrics, Chicago, Illinois;
University of South Alabama College of Medicine, Department of Pharmacology, Mobile, Alabama;
Am J Physiol Lung Cell Mol Physiol. 2014 Jun 1;306(11):L962-74. doi: 10.1152/ajplung.00073.2014. Epub 2014 Apr 18.
An explosion of new information about mitochondria reveals that their importance extends well beyond their time-honored function as the "powerhouse of the cell." In this Perspectives article, we summarize new evidence showing that mitochondria are at the center of a reactive oxygen species (ROS)-dependent pathway governing the response to hypoxia and to mitochondrial quality control. The potential role of the mitochondrial genome as a sentinel molecule governing cytotoxic responses of lung cells to ROS stress also is highlighted. Additional attention is devoted to the fate of damaged mitochondrial DNA relative to its involvement as a damage-associated molecular pattern driving adverse lung and systemic cell responses in severe illness or trauma. Finally, emerging strategies for replenishing normal populations of mitochondria after damage, either through promotion of mitochondrial biogenesis or via mitochondrial transfer, are discussed.
线粒体的新信息不断涌现,揭示了它们的重要性远远超出了其作为“细胞的动力工厂”的悠久功能。在这篇观点文章中,我们总结了新的证据,表明线粒体是一种活性氧(ROS)依赖性途径的中心,该途径控制着对缺氧和线粒体质量控制的反应。还强调了线粒体基因组作为一种哨兵分子,调节肺细胞对 ROS 应激的细胞毒性反应的潜在作用。此外,还关注了受损线粒体 DNA 的命运,以及它作为一种损伤相关分子模式,在严重疾病或创伤中驱动肺部和全身细胞的不良反应。最后,讨论了在损伤后通过促进线粒体生物发生或通过线粒体转移来补充正常线粒体群体的新兴策略。