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PMID: 10318903 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Oxygen sensing in yeast: evidence for the involvement of the respiratory chain in regulating the transcription of a subset of hypoxic genes.

Kwast KE, Burke PV, Staahl BT, Poyton RO

Abstract

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, we 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 CO-binding hemoproteins (cytochrome c oxidase and flavohemoglobin), respiratory inhibitors, and cob1 and rho0 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.

MeSH Terms
Aerobiosis/genetics Antimycin A/pharmacology Carbon Monoxide/pharmacology Cobalt/pharmacology Cytochrome c Group/genetics,metabolism Cytochromes c Electron Transport Complex IV/genetics,metabolism Fatty Acid Desaturases/genetics,metabolism Gene Expression Regulation, Fungal/drug effects,genetics Genes, Fungal Hemeproteins/metabolism Mutation Nickel/pharmacology Oxygen/metabolism Potassium Cyanide/pharmacology RNA, Messenger/analysis Saccharomyces cerevisiae/genetics,metabolism Stearoyl-CoA Desaturase
Chemicals
Cytochrome c Group Hemeproteins RNA, Messenger iso-2-cytochrome C Cobalt Antimycin A Nickel Carbon Monoxide Cytochromes c Fatty Acid Desaturases Stearoyl-CoA Desaturase delta-9 fatty acid desaturase Electron Transport Complex IV Potassium Cyanide Oxygen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kwast K E
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
Burke P V
Staahl B T
Poyton R O
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-05-11
Pages
5446-51
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21879
Subset
IM
Grants
NIGMS NIH HHS · R01 GM030228 · United States
NIGMS NIH HHS · GM30228 · United States
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