Effects of anoxia and the mitochondrion on expression of aerobic nuclear COX genes in yeast -: Evidence for a signaling pathway from the mitochondrial genome to the nucleus
Effects of anoxia and the mitochondrion on expression of aerobic nuclear COX genes in yeast -: Evidence for a signaling pathway from the mitochondrial genome to the nucleus
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DOI：
10.1074/jbc.m009180200
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发表时间：
2001-03-09
影响因子：
4.8
通讯作者：
Poyton, RO
中科院分区：
文献类型：
--
作者：
Dagsgaard, C;Taylor, LE;Poyton, RO
真核细胞至少含有两类氧调节核基因：需氧基因和低氧基因。缺氧诱导低氧基因，而有氧基因下调。近年来，有报道称，哺乳动物和酵母中某些低氧核基因的诱导需要线粒体呼吸，而细胞色素氧化酶在此过程中起着氧传感器的作用。我们已经发现，这些基因在缺氧细胞中的下调反映在其亚基多肽的水平降低，并且细胞色素e氧化酶亚基I、II、III、Vb、VI、VII和VIIa存在于缺氧细胞的原线粒体中。通过使用核cor突变体和线粒体rho（o）和mit（-）突变体，我们发现，在暴露于缺氧的细胞中，这些基因的下调既不需要呼吸作用，也不需要细胞色素e氧化酶，但在常氧和缺氧条件下，它们的完全表达需要线粒体基因组。这种对线粒体基因组的需求与功能性全细胞色素c氧化酶的存在或不存在无关。我们还发现，这些基因在暴露于缺氧的细胞中的下调和由线粒体基因组的不存在引起的下调是彼此独立的。这些发现表明线粒体基因组独立于呼吸和氧化磷酸化作用，影响有氧核考克斯基因的表达，并表明存在从线粒体基因组到核的信号传导途径，
Eucaryotic cells contain at least two general classes of oxygen-regulated nuclear genes: aerobic genes and hypoxic genes. Hypoxic genes are induced upon exposure to anoxia while aerobic genes are down-regulated. Recently, it has been reported that induction of some hypoxic nuclear genes in mammals and yeast requires mitochondrial respiration and that cytochrome-e oxidase functions as an oxygen sensor during this process, In this study, we have examined the role of the mitochondrion and cytochrome-e oxidase in the expression of yeast aerobic nuclear COX genes. We have found that the down-regulation of these genes in anoxic cells is reflected in reduced levels of their subunit polypeptides and that cytochrome-e oxidase subunits I, II, III, Vb, VI, VII, and VIIa are present in promitochondria from anoxic cells. By using nuclear cor mutants and mitochondrial rho(o) and mit(-) mutants, we have found that neither respiration nor cytochrome-e oxidase is required for the down-regulation of these genes in cells exposed to anoxia but that a mitochondrial genome is required for their full expression under both normoxic and anoxic conditions. This requirement for a mitochondrial genome is unrelated to the presence or absence of a functional holocytochrome-c oxidase, We have also found that the down-regulation of these genes in cells exposed to anoxia and the down-regulation that results from the absence of a mitochondrial genome are independent of one another. These findings indicate that the mitochondrial genome, acting independently of respiration and oxidative phosphorylation, affects the expression of the aerobic nuclear COX genes and suggest the existence of a signaling pathway from the mitochondrial genome to the nucleus,