Oxygen sensing in yeast: Evidence for the involvement of the respiratory chain in regulating the transcription of a subset of hypoxic genes
Oxygen sensing in yeast: Evidence for the involvement of the respiratory chain in regulating the transcription of a subset of hypoxic genes
复制标题
DOI：
10.1073/pnas.96.10.5446
复制
发表时间：
1999-05-11
影响因子：
11.1
通讯作者：
Poyton, RO
中科院分区：
文献类型：
--
作者：
Kwast, KE;Burke, PV;Poyton, RO
氧的可用性影响几乎所有生物体中许多基因的转录。虽然感知氧气的分子机制还不清楚，但血红素被认为起着关键作用。在这里，我解决的可能性，氧气传感酵母，在哺乳动物中，涉及氧化还原敏感血红素蛋白。我们发现，一氧化碳（CO）完全阻断缺氧诱导的两个缺氧基因，OLE 1和CYC 7的表达，部分阻断第三个基因，COX 5 b的诱导，并对其他缺氧或有氧基因的表达没有影响。此外，过渡金属（钴和镍）诱导表达的OLE 1和CYC 7在浓度依赖性的方式在有氧条件下。这些研究结果表明，氧化还原状态的氧结合血红素蛋白参与控制至少两个缺氧酵母基因的表达。通过使用两种主要的酵母GO结合血红素蛋白（细胞色素c氧化酶和黄素血红蛋白）、呼吸抑制剂以及cob 1和rho（0）突变体中的每一种缺陷的突变体，我们发现呼吸链参与了这两种基因的缺氧诱导，并且细胞色素c氧化酶可能是血红素蛋白的传感器。“我们的研究结果还表明，酵母中至少有两类缺氧基因（CO敏感和CO不敏感），并暗示多种途径/机制参与调节缺氧酵母基因的表达。
Oxygen availability affects the transcription of a number of genes in nearly all organisms. Although the molecular mechanisms for sensing oxygen are not precisely known, heme is thought to play a pivotal role. Here, me address the possibility that oxygen sensing in yeast, as in mammals, involves a redox-sensitive hemoprotein. We have found that carbon monoxide (CO) completely blocks the anoxia-induced expression of two hypoxic genes, OLE1 and CYC7, partially blocks the induction of a third gene, COX5b, and has no effect on the expression of other hypoxic or aerobic genes. In addition, transition metals (Co and Ni) induce the expression of OLE1 and CYC7 in a concentration-dependent manner under aerobic conditions. These findings suggest that the redox state of an oxygen-binding hemoprotein is involved in controlling the expression of at least two hypoxic yeast genes. By using mutants deficient in each of the two major yeast GO-binding hemoproteins (cytochrome c oxidase and flavohemoglobin), respiratory inhibitors, and cob1 and rho(0) mutants, we have found that the respiratory chain is involved in the anoxic induction of these two genes and that cytochrome c oxidase is likely the hemoprotein "sensor." Our findings also indicate that there are at least two classes of hypoxic genes in yeast (CO sensitive and CO insensitive) and imply that multiple pathways/mechanisms are involved in modulating the expression of hypoxic yeast genes.