Lipoproteins and Atherosclerosis Group, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 1V1, Canada.
Curr Biol. 2012 Jan 24;22(2):135-41. doi: 10.1016/j.cub.2011.11.057. Epub 2012 Jan 5.
Mitochondrial respiration relies on electron transport, an essential yet dangerous process in that it leads to the generation of reactive oxygen species (ROS). ROS can be neutralized within the mitochondria through enzymatic activity, yet the mechanism for steady-state removal of oxidized mitochondrial protein complexes and lipids is not well understood. We have previously characterized vesicular profiles budding from the mitochondria that carry selected cargo. At least one population of these mitochondria-derived vesicles (MDVs) targets the peroxisomes; however, the fate of the majority of MDVs was unclear. Here, we demonstrate that MDVs carry selected cargo to the lysosomes. Using a combination of confocal and electron microscopy, we observe MDVs in steady state and demonstrate that they are stimulated as an early response to oxidative stress, the extent of which is determined by the respiratory status of the mitochondria. Delivery to the lysosomes does not require mitochondrial depolarization and is independent of ATG5 and LC3, suggesting that vesicle delivery complements mitophagy. Consistent with this, ultrastructural analysis of MDV formation revealed Tom20-positive structures within the vesicles of multivesicular bodies. These data characterize a novel vesicle transport route between the mitochondria and lysosomes, providing insights into the basic mechanisms of mitochondrial quality control.
线粒体呼吸依赖于电子传递，这是一个必不可少但又很危险的过程，因为它会导致活性氧物种（ROS）的产生。ROS 可以通过酶的活性在 线粒体 内被中和，但对于氧化的 线粒体 蛋白复合物和脂质的稳态去除机制还不是很清楚。我们之前已经对从 线粒体 出芽的囊泡进行了特征描述，这些囊泡携带特定的货物。这些 线粒体 衍生的囊泡（MDVs）中至少有一部分靶向过氧化物酶体；然而，大多数 MDVs 的命运尚不清楚。在这里，我们证明 MDVs 将选定的货物携带到溶酶体。我们结合使用共聚焦和电子显微镜，观察到了 稳定状态下的 MDVs，并证明它们作为对氧化应激的早期反应而被刺激，其程度取决于 线粒体 的呼吸状态。到溶酶体的运输不需要 线粒体 去极化，并且不依赖于 ATG5 和 LC3，这表明囊泡的运输补充了线粒体自噬。与此一致的是，对 MDV 形成的超微结构分析显示，多泡体的囊泡内存在 Tom20 阳性结构。这些数据描绘了 线粒体 和溶酶体之间的一种新的囊泡运输途径，为 线粒体 质量控制的基本机制提供了新的见解。
