Department of Biochemistry and Food Science, Faculty of Agricultural, Food, and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel.
J Biol Chem. 2009 Dec 18;284(51):35885-95. doi: 10.1074/jbc.M109.048140.
Mitophagy is an autophagic process that degrades mitochondria by an intracellular engulfment that leads to their delivery into the lumen of the cell's hydrolytic compartment, such as the lysosome in animal cells or the vacuole in yeast. It is hypothesized that such processes serve a quality control function to prevent or slow the accumulation of malfunctioning mitochondria, which are thought in turn to underlie central aspects of the aging process in eukaryotic organisms. We recently identified a conserved mitochondrial protein phosphatase homolog, Aup1, which is required for efficient stationary phase mitophagy in yeast. In the present report, we demonstrate that the retrograde signaling pathway (RTG) is defective in aup1Delta mutants. In agreement with a role for Aup1 in the regulation of the RTG pathway, we find that deletion of RTG3, a transcription factor that mediates the RTG response, causes a defect in stationary phase mitophagy and that deletion of AUP1 leads to changes in Rtg3 phosphorylation patterns under these conditions. In addition, we find that mitophagic conditions lead to induction of RTG pathway target genes in an Aup1-dependent fashion. Thus, our results suggest that the function of Aup1 in mitophagy could be explained through its regulation of Rtg3-dependent transcription.
自噬是一种通过细胞内吞噬作用降解线粒体的自噬过程，导致它们被递送到细胞的水解隔室的腔中，如动物细胞中的溶酶体或酵母中的液泡。据推测，这些过程具有质量控制功能，以防止或减缓功能失调的线粒体的积累，而这些线粒体被认为是真核生物衰老过程的核心方面的基础。我们最近鉴定了一种保守的线粒体蛋白磷酸酶同源物 Aup1，它是酵母中有效静止期自噬所必需的。在本报告中，我们证明了 aup1Δ突变体中的逆行信号通路（RTG）有缺陷。与 Aup1 在 RTG 途径调节中的作用一致，我们发现删除 RTG3（一种介导 RTG 反应的转录因子）会导致静止期自噬缺陷，并且在这些条件下删除 AUP1 会导致 Rtg3 磷酸化模式发生变化。此外，我们发现自噬条件会以依赖于 Aup1 的方式诱导 RTG 途径靶基因的表达。因此，我们的结果表明，Aup1 在自噬中的功能可以通过其对 Rtg3 依赖性转录的调节来解释。
