Oxygen and Catabolite Regulation of Hemoprotein Biosynthesis in Yeast

Mattoon, James R.; Lancashire, William E.; Sanders, Hildagarde K.; Carvajal, Elvira; Malamud, Dulce R.; Braz, Glória R.C.; Panek, Anita D.

doi:10.1016/b978-0-12-164380-5.50030-x

Cited by 48 publications

(50 citation statements)

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“…The remaining four enzymes involved in heme synthesis are localized in the cytosol [1,3,4]. The control of heme biosynthesis is complex and is dependent on multiple factors, including cell type and the availability of substrates [5][6][7]. Heme synthesis requires the key precursor 5-aminolevulinic acid (ALA) and two substrates, oxygen and ferrous iron (Fe 2+ ) ( Figure 1, Table 1) [1,3,7].…”

Section: Introductionmentioning

confidence: 99%

“…The availability of each of these molecules may be limiting and may dictate the rate of heme synthesis, under certain circumstances [7]. For example, in yeast, heme synthesis is under the control of oxygen level [3,5,8]. Oxygen is not only required for the two steps that use it as a substrate, but its level also determines the activity of ferrochelatase, the last enzyme involved in heme synthesis ( Figure 1) [8].…”

Section: Introductionmentioning

confidence: 99%

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Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

2006

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

2006

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“…In bakers' yeast (Saccharomyces cerevisiae), the synthesis of respiratory chain components and enzymes of the citric acid cycle is repressed in the absence of oxygen or in the presence of glucose (9,18,24,25). The reverse of this process, the derepression of mitochondrial enzymes, is most easily monitored spectroscopically by the reappearance of cytochromes, but the synthesis of many achromatic mitochondrial enzymes is also stimulated by the removal of glucose from the culture medium or by the introduction of air to an anaerobic culture.…”

mentioning

confidence: 99%

Derepression of citrate synthase in Saccharomyces cerevisiae may occur at the level of transcription.

Hoosein¹,

Lewin²

1984

Mol. Cell. Biol.

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Pulse-chase labeling in whole cells and cell-free protein synthesis were l,ed to The level of mitochondrial enzymes is finely tuned to the energy demands of the cell. In bakers' yeast (Saccharomyces cerevisiae), the synthesis of respiratory chain components and enzymes of the citric acid cycle is repressed in the absence of oxygen or in the presence of glucose (9,18,24,25). The reverse of this process, the derepression of mitochondrial enzymes, is most easily monitored spectroscopically by the reappearance of cytochromes, but the synthesis of many achromatic mitochondrial enzymes is also stimulated by the removal of glucose from the culture medium or by the introduction of air to an anaerobic culture. Recent evidence suggests that synthesis of iso-1-cytochrome c in S. cereivisiae is regulated at the stage of transcription by the availability of heme (10, 30).We have studied the induction of citrate synthase (citrate oxaloacetate lyase, EC 4.1.3.7) during the growth of yeast cells in the presence of glucose. In Nelurospora crassa, this enzyme is made in the cytoplasm as a larger precursor which is processed to a Fmaller mature form as it is imported into the mitochondrion (12). Preliminary reports suggest that a similar mode of synthesis and transport occurs in S. cerevisiae (2). Like many other yeast mitochondrial proteins (21), citrate synthase is made primarily on "free" polyribosomes in the cytoplasm and is transported into the organelle independently of protein synthesis (28). Our interest in this enzyme was stimulated by the report (25) that citrate synthase activity can be derepressed in S. cerevisiae even in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. This result may reflect the presence of a pool of latent enzyme whose activity can be induced by the appropriate stimulus.We have begun by investigating whether the derepression of citrate synthase occurs at the level of transcription. We report that the amount of translatable RNA which encodes a precursor form of citrate synthase increases as the enzyme level is induced.MATERIALS AND METHODS S. cerevisiae strains and growth conditions. Two haploid S. cerevisiae strains were employed in this study. These were D273-1OB (MA To, ATCC 25657) and D273-10B/la, a [rho-] Purification of citrate synthase. Citrate synthase was purified from isolated S. cerevisiae mitochrondria by affinity elution chromatography (5, 19), using a modification of the method of Davies and Scopes (5). We replaced the carboxymethyl cellulose chromatography with a Biorex 70 column in the same buffer system. Nearly all of the loaded citrate synthase activity was bound to the column, and no activity could be measured in either of the wash fractions. Final specific activity of the isolated enzyme was greater than 1,400 U/mg of protein and represented a 150-fold purification over the crude lysate. Enzyme units are defined as micromoles of reduced coenzyme A formed per minute and were assayed by the method of Parvin (22).Antibodies to citrate synthase were ...

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“…6B, lanes 2 and 8) and even significant transcriptional activity (49). However, in cells grown anoxically, heme synthesis is greatly limited (30,60). Thus, Hap1 is inactive in anoxically grown cells (Figs.…”

Section: Discussionmentioning

confidence: 97%

“…6). Because heme synthesis is greatly limited under anoxic conditions (30,60), Hap1 instability in extracts prepared from cells grown under anoxic conditions (Fig. 6A) is likely due to heme deficiency in these cells.…”

Section: Discussionmentioning

confidence: 99%

A Mechanism of Oxygen Sensing in Yeast

Hon

Dodd

Dirmeier

et al. 2003

Journal of Biological Chemistry

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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 doseresponse curves as Hap1-dependent aerobic genes and that these dose-response curves have a sharp break at ϳ1 M O 2 . 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.The transcription of many genes in both prokaryotes and eukaryotes is affected by the presence or absence of oxygen and by oxygen concentration itself (1-4). These oxygen-regulated genes can be placed into one of two broad groups: aerobic genes, which are transcribed optimally under aerobic conditions, and hypoxic genes, which are optimally expressed under anoxic or hypoxic conditions. Although considerable progress has been made in identifying oxygen-responsive transcription factors in eukaryotes, the molecular mechanisms by which oxygen sensors directly sense oxygen concentration remain to be further elucidated (1,5). Understanding the molecular mechanism of oxygen sensing is of fundamental biological and biomedical importance, because oxygen sensing is directly related to many diverse physiological and pathological processes, such as erythropoiesis, angiogenesis, wound healing, and ischemia (1, 6 -12).In mammalian cells, a family of hypoxia-inducible transcription factors (HIFs) 1 has been shown to mediate oxygen regulation of many genes (13). Although these HIFs do not directly sense oxygen levels, recent findings have suggested that two enzymes, prolyl hydroxylase (6, 14) and asparaginyl hydroxylase (15, 16), which use oxygen as a substrate to modify the ␣ subunit of HIF1 and cause its inactivation or degradation, could function as oxygen sensors, it has yet to be shown that these prolyl and asparaginyl hydroxylases sense oxygen or changes in oxygen concentration.In yeast, several different kinds of oxygen-responsive transcription factors have been identified. These factors include Rox1, which represses transcription of hypoxic genes under aerobic conditions (17); Mga2, which activa...

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Oxygen and Catabolite Regulation of Hemoprotein Biosynthesis in Yeast

Cited by 48 publications

References 35 publications

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

Derepression of citrate synthase in Saccharomyces cerevisiae may occur at the level of transcription.

A Mechanism of Oxygen Sensing in Yeast

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