Aup1p, a yeast mitochondrial protein phosphatase homolog, is required for efficient stationary phase mitophagy and cell survival
Aup1p, a yeast mitochondrial protein phosphatase homolog, is required for efficient stationary phase mitophagy and cell survival
复制标题
DOI：
10.1074/jbc.m605940200
复制
发表时间：
2007-02-23
影响因子：
4.8
通讯作者：
Abeliovich, Hagai
中科院分区：
文献类型：
--
作者：
Tal, Ruth;Winter, Gal;Abeliovich, Hagai
自噬是发生在所有真核细胞中的分解代谢膜运输过程，导致液泡或溶酶体腔内胞质物质的水解降解。线粒体自噬是一种靶向线粒体的选择性自噬形式，目前对其了解甚少。最近的一些报道表明，线粒体自噬是一种选择性的过程，其目标是受损的线粒体，而其他研究表明，线粒体自噬在细胞死亡过程中起作用。在筛选与酵母中自噬专用蛋白激酶Atg1p功能相互作用的蛋白磷酸酶同源物时，我们发现了由酿酒酵母阅读框YCR079w编码的Aup1p。Aup1p与动物细胞中的蛋白磷酸酶同源物家族高度相似，根据序列分析，该家族被预测定位于线粒体。有趣的是，我们发现Aulp1p定位于线粒体膜间空间，是固定期细胞有效的线粒体自噬所必需的。活力研究表明，在长时间的固定期培养中，Aup1p是细胞有效存活所必需的，这意味着在我们的工作条件下，有丝分裂具有促进存活的作用。我们的数据表明，Aup1p可能是信号转导机制的一部分，标志着线粒体被隔离到自噬体中。
Autophagy is a catabolic membrane-trafficking process that occurs in all eukaryotic cells and leads to the hydrolytic degradation of cytosolic material in the vacuolar or lysosomal lumen. Mitophagy, a selective form of autophagy targeting mitochondria, is poorly understood at present. Several recent reports suggest that mitophagy is a selective process that targets damaged mitochondria, whereas other studies imply a role for mitophagy in cell death processes. In a screen for protein phosphatase homologs that functionally interact with the autophagy-dedicated protein kinase Atg1p in yeast, we have identified Aup1p, encoded by Saccharomyces cerevisiae reading frame YCR079w. Aup1p is highly similar to a family of protein phosphatase homologs in animal cells that are predicted to localize to mitochondria based on sequence analysis. Interestingly, we found that Aulp1p localizes to the mitochondrial intermembrane space and is required for efficient mitophagy in stationary phase cells. Viability studies demonstrate that Aup1p is required for efficient survival of cells in prolonged stationary phase cultures, implying a pro-survival role for mitophagy under our working conditions. Our data suggest that Aup1p may be part of a signal transduction mechanism that marks mitochondria for sequestration into autophagosomes.