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A mechanism of oxygen sensing in yeast M ... ic pathway affect Hap1 activity
A mechanism of oxygen sensing in yeast. Multiple oxygen-responsive steps in the heme biosynthetic pathway affect Hap1 activity.
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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 approximately 1 microM 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.
Hon T, Dodd A, Dirmeier R, Gorman N, Sinclair PR, Zhang L, Poyton RO
The Journal of biological chemistry
2003-12-12 00:00
278
50
50771-80
Blotting, Western,Cell Division,DNA-Binding Proteins,Dose-Response Relationship, Drug,Ferrochelatase,Heme,Models, Chemical,Oxygen,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Time Factors,Trans-Activators,DNA-Binding Proteins,HAP1 protein, S cerevisiae,Saccharomyces cerevisiae Proteins,Trans-Activators,Heme,Oxygen,Ferrochelatase
Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA
J. Biol. Chem.
NIEHS ES06263, NIGMS GM30228, NIGMS GM62246, NHLBI HL63324, NHLBI HL65568
0021-9258
10.1074/jbc.M303677200
M303677200
1010
True
14512429
