Faculty of Biology, LMU Munich, 82152 Planegg-Martinsried, Germany.
Faculty of Biology, LMU Munich, 82152 Planegg-Martinsried, Germany.
Cell Rep. 2019 Aug 13;28(7):1659-1669.e5. doi: 10.1016/j.celrep.2019.07.049.
The induction of the mitochondrial unfolded protein response (UPR) results in increased transcription of the gene encoding the mitochondrial chaperone HSP70. We systematically screened the C. elegans genome and identified 171 genes that, when knocked down, induce the expression of an hsp-6 HSP70 reporter and encode mitochondrial proteins. These genes represent many, but not all, mitochondrial processes (e.g., mitochondrial calcium homeostasis and mitophagy are not represented). Knockdown of these genes leads to reduced mitochondrial membrane potential and, hence, decreased protein import into mitochondria. In addition, it induces UPR in a manner that is dependent on ATFS-1 but that is not antagonized by the kinase GCN-2. We propose that compromised mitochondrial protein import signals the induction of UPR and that the mitochondrial targeting sequence of ATFS-1 functions as a sensor for this signal.
线粒体未折叠蛋白反应（UPR）的诱导导致编码线粒体伴侣 HSP70 的基因转录增加。我们系统地筛选了秀丽隐杆线虫的基因组，鉴定出 171 个基因，当这些基因被敲低时，会诱导 hsp-6 HSP70 报告基因的表达，并编码线粒体蛋白。这些基因代表了许多（但不是全部）线粒体过程（例如，线粒体钙稳态和线粒体自噬未被代表）。这些基因的敲低导致线粒体膜电位降低，从而减少蛋白质向线粒体的输入。此外，它以一种依赖于 ATFS-1 但不受激酶 GCN-2 拮抗的方式诱导 UPR。我们提出，受损的线粒体蛋白输入信号诱导 UPR，而 ATFS-1 的线粒体靶向序列作为该信号的传感器发挥作用。
