Abeliovich Hagai
Department of Biochemistry and Food Science, Faculty of Agricultural, Food, and Environmental Quality Sciences, Hebrew University of Jerusalem, Israel.
Autophagy. 2007 May-Jun;3(3):275-7. doi: 10.4161/auto.3915. Epub 2007 May 29.
The degradation and recycling of mitochondria is an important household chore in eukaryotic cells. It is thought that mitochondrial autophagy, or mitophagy, is the major route by which mitochondria are degraded. In this view, the cell would selectively induce mitophagy to expunge malfunctioning mitochondria, thus ridding the cell of troublesome sources of reactive oxygen species, apoptosis-inducing factors, or unnecessary metabolic burden. This standard view of mitophagy, in addition to some experimental reports, points to a pro-survival role of mitophagy. However, there is also a significant amount of evidence that suggests a pro-death role of this process, some of it coming from studies in yeast. Aup1 is a protein phosphatase homolog that shows a genetic interaction with the Atg1 protein kinase, localizes to mitochondria, and is required for mitophagy under stationary phase conditions in lactate medium. In contrast with previous yeast studies on mitophagy, deletion of AUP1 results in decreased viability under mitophagy-inducing conditions, suggesting a pro-survival role under physiologically relevant conditions. Thus, the Janus-faced nature of mitophagy is conserved between yeast and mammalian systems.
线粒体的降解与循环利用是真核细胞中一项重要的内部事务。人们认为线粒体自噬,即线粒体吞噬,是线粒体降解的主要途径。按照这种观点,细胞会选择性地诱导线粒体吞噬以清除功能异常的线粒体,从而使细胞摆脱活性氧、凋亡诱导因子或不必要代谢负担等麻烦来源。除了一些实验报告外,这种线粒体吞噬的标准观点表明其具有促生存作用。然而,也有大量证据表明这一过程具有促死亡作用,其中一些来自酵母研究。Aup1是一种蛋白磷酸酶同源物,它与Atg1蛋白激酶存在遗传相互作用,定位于线粒体,并且在乳酸培养基的稳定期条件下线粒体吞噬过程中是必需的。与之前关于酵母线粒体吞噬的研究不同,AUP1的缺失导致在诱导线粒体吞噬的条件下细胞活力下降,这表明在生理相关条件下其具有促生存作用。因此,线粒体吞噬的双面性在酵母和哺乳动物系统中是保守的。