Cited by 175Fungal and yeast genetics researchCancer, Hypoxia, and MetabolismHemoglobin structure and function

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

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Kwast, Kurt E., Burke, Patricia V., Staahl, Brett T., Poyton, Robert O.·1999·Proceedings of the National Academy of Sciences

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.

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  • A decrease in oxygen bioavailability causes a drop in heme and ergosterol levels that triggers the activation of signaling pathways that induce the expression of both hypoxic and ERG genes.

    “Conversely, a decrease in oxygen bioavailability causes a drop in heme and ergosterol levels that triggers the activation of signaling pathways that induce the expression of both hypoxic and ERG genes [94].”
  • Several genome-wide expression studies under low oxygen conditions have reflected that the pattern of expression differs among ERG genes, although some general trends can be extracted.

    “Several genome-wide expression studies based on microarray and RNA-Seq analyses under low oxygen conditions have reflected that the pattern of expression differs among ERG genes, although some general trends can be extracted [94,96,98,100,101,102,103].”

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Authors
Kwast, K. E., Burke, P. V., Staahl, B. T., & Poyton, R. O.
Affiliations
  • University of Colorado Boulder (US)
  • Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347
Venue
Proceedings of the National Academy of Sciences
Published
1999-05-11
Volume
96
Issue
10
Pages
5446-5451
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2168009569
Cited by
175
References
66
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 8 · 2012: 12
FWCI
3.91
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM 30228, R01GM030228)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
oxygen sensing, hypoxic gene expression, Saccharomyces cerevisiae, cytochrome c oxidase, flavohemoglobin, carbon monoxide, electron transport chain, heme, OLE1, COX5B, cobalt, nickel, anoxia, transcriptional regulation
MeSH terms
Aerobiosis, Antimycin A, Carbon Monoxide, Cobalt, Cytochrome c Group, Electron Transport Complex IV, Genes, Fungal, Hemeproteins, Mutation, Nickel, Oxygen, Potassium Cyanide, RNA, Messenger, Saccharomyces cerevisiae, Stearoyl-CoA Desaturase, Gene Expression Regulation, Fungal, Fatty Acid Desaturases, Cytochromes c

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