Kanki Tomotake, Wang Ke, Cao Yang, Baba Misuzu, Klionsky Daniel J
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Dev Cell. 2009 Jul;17(1):98-109. doi: 10.1016/j.devcel.2009.06.014.
Mitochondrial quality control is important in maintaining proper cellular homeostasis. Although selective mitochondrial degradation by autophagy (mitophagy) is suggested to have an important role in quality control, and though there is evidence for a direct relation between mitophagy and neurodegenerative diseases, the molecular mechanism of mitophagy is poorly understood. Using a screen for mitophagy-deficient mutants, we found that YIL146C/ECM37 is essential for mitophagy. This gene is not required for other types of selective autophagy or for nonspecific macroautophagy. We designated this autophagy-related (ATG) gene as ATG32. The Atg32 protein localizes on mitochondria. Following the induction of mitophagy, Atg32 binds Atg11, an adaptor protein for selective types of autophagy, and is then recruited to and imported into the vacuole along with mitochondria. Therefore, Atg32 confers selectivity for mitochondrial sequestration as a cargo and is necessary for recruitment of this organelle by the autophagy machinery for mitophagy.
线粒体质量控制对于维持细胞内环境稳定至关重要。尽管自噬（线粒体自噬）介导的选择性线粒体降解被认为在质量控制中发挥重要作用，并且有证据表明线粒体自噬与神经退行性疾病之间存在直接关联，但线粒体自噬的分子机制仍知之甚少。通过筛选线粒体自噬缺陷型突变体，我们发现YIL146C/ECM37对于线粒体自噬至关重要。该基因对于其他类型的选择性自噬或非特异性巨自噬并非必需。我们将这个自噬相关（ATG）基因命名为ATG32。Atg32蛋白定位于线粒体。在线粒体自噬诱导后，Atg32与Atg11结合，Atg11是一种用于选择性自噬类型的衔接蛋白，随后Atg32与线粒体一起被招募并导入液泡。因此，Atg32作为货物赋予线粒体隔离的选择性，并且对于自噬机制招募该细胞器进行线粒体自噬是必需的。
