Okamoto Koji, Kondo-Okamoto Noriko, Ohsumi Yoshinori
Division of Molecular Cell Biology, National Institute for Basic Biology, Okazaki, Japan.
Dev Cell. 2009 Jul;17(1):87-97. doi: 10.1016/j.devcel.2009.06.013.
Mitochondria are essential organelles that produce most of the energy for a cell, but concomitantly accumulate oxidative damage. Degradation of damaged mitochondria is critical for cell homeostasis, and this process is thought to be mediated by mitophagy, an autophagy-related pathway specific for mitochondria. However, whether mitochondria are selectively degraded, and how the autophagic machinery is targeted to mitochondria, remain largely unknown. Here we demonstrate that, in post-log phase cells under respiratory conditions, a substantial fraction of mitochondria are exclusively sequestered as cargoes and transported to the vacuole, a lytic compartment in yeast, in an autophagy-dependent manner. Interestingly, we found Atg32, a mitochondria-anchored protein essential for mitophagy that is induced during respiratory growth. In addition, our data suggest that Atg32 interacts with Atg8 and Atg11, autophagy-related proteins critical for recognition of cargo receptors. We propose that Atg32 acts as a mitophagy-specific receptor and regulates selective degradation of mitochondria.
线粒体是为细胞产生大部分能量的重要细胞器，但同时也会积累氧化损伤。受损线粒体的降解对细胞稳态至关重要，这一过程被认为是由线粒体自噬介导的，线粒体自噬是一种与自噬相关的、专门针对线粒体的途径。然而，线粒体是否被选择性降解，以及自噬机制如何靶向线粒体，在很大程度上仍然未知。在这里，我们证明，在呼吸条件下的对数后期细胞中，相当一部分线粒体以自噬依赖的方式被专门隔离为货物并运输到液泡（酵母中的一种溶酶体区室）中。有趣的是，我们发现了Atg32，一种在呼吸生长过程中被诱导的、对线粒体自噬至关重要的线粒体锚定蛋白。此外，我们的数据表明Atg32与Atg8和Atg11相互作用，Atg8和Atg11是对货物受体识别至关重要的自噬相关蛋白。我们提出Atg32作为线粒体自噬特异性受体并调节线粒体的选择性降解。
