EFFECTS OF OXYGEN CONCENTRATION ON THE EXPRESSION OF CYTOCHROME-C ANDCYTOCHROME-C-OXIDASE GENES IN YEAST

Oxygen is an important environmental regulator for the transcription o f several genes in Saccharomyces cerevisiae, but it is not yet clear h ow this yeast or other eukaryotes actually sense oxygen. To begin to a ddress this we have examined the effects of oxygen concentration on th e expression of several nuclear genes (CYC1, CYC7, COX4, COX5a, COX5b, COX6, COX7, COX8, and COX9) for proteins of the terminal portion of t he respiratory chain. COX5b and CYC7 are hypoxic genes; the rest are a erobic genes. We have found that the level of expression of these gene s is determined by oxygen concentration per se and not merely the pres ence or absence of oxygen and that each of these genes has a low oxyge n threshold (0.5-1 mu M O-2) for expression. For some aerobic genes (C OX4, COX5a, COX7, COX8, and COX9) there is a gradual decline in expres sion between 200 mu M O-2 (air) and their oxygen threshold. Below this threshold expression drops precipitously. For others (COX5a and CYC1) the level of expression is nearly constant between 200 mu M O-2 and t heir threshold and then drops off. The hypoxic genes COX5b and CYC7 ar e not expressed until the oxygen concentration is below 0.5 mu M O-2. These studies have also revealed that COX5a and CYC1, the genes for th e aerobic isoforms of cytochrome c oxidase subunit V and cytochrome c, and COX5b and CYC7, the genes for the hypoxic isoforms of cytochrome c oxidase subunit V and cytochrome c, are coexpressed at a variety of oxygen concentrations and switch on or off at extremely low oxygen con centrations. By shifting cells from one oxygen concentration to anothe r we have found that aerobic genes are induced faster than hypoxic gen es and that transcripts from both types of gene are turned over quickl y. These findings have important implications for cytochrome c oxidase function and biogenesis and far models of oxygen sensing in yeast.