HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 50, 50771-50780, December 12, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/50/50771    most recent M303677200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hon, T. Articles by Poyton, R. O. Search for Related Content PubMed PubMed Citation Articles by Hon, T. Articles by Poyton, R. O. Social Bookmarking                      What's this?

A Mechanism of Oxygen Sensing in Yeast

MULTIPLE OXYGEN-RESPONSIVE STEPS IN THE HEME BIOSYNTHETIC PATHWAY AFFECT Hap1 ACTIVITY^*

Thomas Hon, Athena Dodd, Reinhard Dirmeier, Nadia Gorman¶, Peter R. Sinclair¶, Li Zhang||, and Robert O. Poyton

From the Department of Biochemistry, New York University School of Medicine, New York, New York 10016, the Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, and the ^¶Department of Biochemistry and Pharmacology, Veterans Affairs Medical Center and Dartmouth Medical School, White River Junction, Vermont 05009

Heme plays central roles in oxygen sensing and utilization in many living organisms. In yeast, heme mediates the effect of oxygen on the expression of many genes involved in using or detoxifying oxygen. However, a direct link between intracellular heme level and oxygen concentration has not been vigorously established. In this report, we have examined the relationships among oxygen levels, heme levels, Hap1 activity, and HAP1 expression. We found that Hap1 activity is controlled in vivo by heme and not by its precursors and that heme activates Hap1 even in anoxic cells. We also found that Hap1 activity exhibits the same oxygen dose-response curves as Hap1-dependent aerobic genes and that these dose-response curves have a sharp break at 1 µM O₂. The results show that the intracellular signaling heme level, reflected as Hap1 activity, is closely correlated with oxygen concentration. Furthermore, we found that bypass of all heme synthetic steps but ferrochelatase by deuteroporphyrin IX does not circumvent the need for oxygen in Hap1 full activation by heme, suggesting that the last step of heme synthesis, catalyzed by ferrochelatase, is also subjected to oxygen control. Our results show that multiple heme synthetic steps can sense oxygen concentration and provide significant insights into the mechanism of oxygen sensing in yeast.

Received for publication, April 9, 2003 , and in revised form, September 17, 2003.

^* This work was supported by National Institutes of Health Grants GM62246, HL65568 (to L. Z.), GM30228, HL63324 (to R. O. P.), and ES06263 and funds from the Department of Veterans Affairs (to P. R. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| A Monique Weill-Caulier Scholar. To whom correspondence should be addressed: Dept. of Biochemistry, New York University School of Medicine 550 First Ave., New York, NY 10016. Tel.: 212-263-8506; Fax: 212-263-8166; E-mail: li.zhang{at}med.nyu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				O. Protchenko, M. Shakoury-Elizeh, P. Keane, J. Storey, R. Androphy, and C. C. Philpott Role of PUG1 in Inducible Porphyrin and Heme Transport in Saccharomyces cerevisiae Eukaryot. Cell, May 1, 2008; 7(5): 859 - 871. [Abstract] [Full Text] [PDF]

				M. J. Hickman and F. Winston Heme Levels Switch the Function of Hap1 of Saccharomyces cerevisiae between Transcriptional Activator and Transcriptional Repressor Mol. Cell. Biol., November 1, 2007; 27(21): 7414 - 7424. [Abstract] [Full Text] [PDF]

				B. S. J. Davies and J. Rine A Role for Sterol Levels in Oxygen Sensing in Saccharomyces cerevisiae Genetics, September 1, 2006; 174(1): 191 - 201. [Abstract] [Full Text] [PDF]

				J. BAILEY-SERRES and R. CHANG Sensing and Signalling in Response to Oxygen Deprivation in Plants and Other Organisms Ann. Bot., September 1, 2005; 96(4): 507 - 518. [Abstract] [Full Text] [PDF]

				B. M. Emerling and N. S. Chandel Oxygen Sensing: Getting Pumped by Sterols Sci. Signal., June 21, 2005; 2005(289): pe30 - pe30. [Abstract] [Full Text] [PDF]

				L.-C. Lai, A. L. Kosorukoff, P. V. Burke, and K. E. Kwast Dynamical Remodeling of the Transcriptome during Short-Term Anaerobiosis in Saccharomyces cerevisiae: Differential Response and Role of Msn2 and/or Msn4 and Other Factors in Galactose and Glucose Media Mol. Cell. Biol., May 15, 2005; 25(10): 4075 - 4091. [Abstract] [Full Text] [PDF]