Dependence of Peroxisomal β-Oxidation on Cytosolic Sources of NADPH

Growth of Saccharomyces cerevisiaewith a fatty acid as carbon source was shown previously to require function of either glucose-6-phosphate dehydrogenase (ZWF1) or cytosolic NADP+-specific isocitrate dehydrogenase (IDP2), suggesting dependence of β-oxidation on a cytosolic source of NADPH. In this study, we find that ΔIDP2ΔZWF1 strains containing disruptions in genes encoding both enzymes exhibit a rapid loss of viability when transferred to medium containing oleate as the carbon source. This loss of viability is not observed following transfer of a ΔIDP3 strain lacking peroxisomal isocitrate dehydrogenase to medium with docosahexaenoate, a nonpermissive carbon source that requires function of IDP3 for β-oxidation. This suggests that the fatty acid− phenotype ofΔIDP2ΔZWF1 strains is not a simple defect in utilization. Instead, we propose that the common function shared by IDP2 and ZWF1 is maintenance of significant levels of NADPH for enzymatic removal of the hydrogen peroxide generated in the first step of peroxisomal β-oxidation in yeast and that inadequate levels of the reduced form of the cofactor can produce lethality. This proposal is supported by the finding that the sensitivity to exogenous hydrogen peroxide previously reported for ΔZWF1 mutant strains is less pronounced when analyses are conducted with a nonfermentable carbon source, a condition associated with elevated expression of IDP2. Under those conditions, similar slow growth phenotypes are observed forΔZWF1 and ΔIDP2 strains, and co-disruption of both genes dramatically exacerbates the H2O2s phenotype. Collectively, these results suggest that IDP2, when expressed, and ZWF1 have critical overlapping functions in provision of reducing equivalents for defense against endogenous or exogenous sources of H2O2. Growth of Saccharomyces cerevisiaewith a fatty acid as carbon source was shown previously to require function of either glucose-6-phosphate dehydrogenase (ZWF1) or cytosolic NADP+-specific isocitrate dehydrogenase (IDP2), suggesting dependence of β-oxidation on a cytosolic source of NADPH. In this study, we find that ΔIDP2ΔZWF1 strains containing disruptions in genes encoding both enzymes exhibit a rapid loss of viability when transferred to medium containing oleate as the carbon source. This loss of viability is not observed following transfer of a ΔIDP3 strain lacking peroxisomal isocitrate dehydrogenase to medium with docosahexaenoate, a nonpermissive carbon source that requires function of IDP3 for β-oxidation. This suggests that the fatty acid− phenotype ofΔIDP2ΔZWF1 strains is not a simple defect in utilization. Instead, we propose that the common function shared by IDP2 and ZWF1 is maintenance of significant levels of NADPH for enzymatic removal of the hydrogen peroxide generated in the first step of peroxisomal β-oxidation in yeast and that inadequate levels of the reduced form of the cofactor can produce lethality. This proposal is supported by the finding that the sensitivity to exogenous hydrogen peroxide previously reported for ΔZWF1 mutant strains is less pronounced when analyses are conducted with a nonfermentable carbon source, a condition associated with elevated expression of IDP2. Under those conditions, similar slow growth phenotypes are observed forΔZWF1 and ΔIDP2 strains, and co-disruption of both genes dramatically exacerbates the H2O2s phenotype. Collectively, these results suggest that IDP2, when expressed, and ZWF1 have critical overlapping functions in provision of reducing equivalents for defense against endogenous or exogenous sources of H2O2. Reducing equivalents in the form of NADPH are essential for many enzymatic steps involved in biosynthesis of cellular macromolecules. NADPH is also the essential cofactor for glutathione- and thioredoxin-dependent enzymes that constitute major cellular defenses against oxidative damage (reviewed in Refs. 1Wells W.W. Yang Y. Deits T.L. Gan Z.-R. Adv. Enzymol. Relat. Areas Mol. Biol. 1993; 66: 149-201PubMed Google Scholar and 2Halliwell B. Nutr. Rev. 1994; 52: 253-265Crossref PubMed Scopus (851) Google Scholar). In eucaryotic cells, the majority of these NADPH-dependent reactions occur in the cytosol. Availability of the reduced form of the cofactor requires maintenance of high steady-state cytosolic redox ratios for NADPH:NADP+ and values as high as ∼70:1 have been reported (3Stryer and sources of NADPH are in In a Biol. PubMed Scopus Google we and phenotype analyses to the by the oxidative of the and by of NADP+-specific isocitrate that yeast are in of enzymatic sources of NADPH for containing disruptions In the growth phenotypes observed the of strains containing of genes encoding glucose-6-phosphate dehydrogenase (ZWF1) and cytosolic NADP+-specific isocitrate dehydrogenase to with fatty as a carbon source and the of ΔIDP2ΔZWF1 strains to this we the fatty acid− growth phenotype by ΔIDP2ΔZWF1 yeast This phenotype is not observed for mutant strains containing a of ZWF1 or of IDP2, and the mutant strain containing both disruptions is of growth on as a carbon source Biol. PubMed Scopus Google Scholar). suggest that ZWF1 and have overlapping function in of β-oxidation of fatty a that is peroxisomal in (reviewed in Refs. Scholar and PubMed Scopus Google of the yeast ZWF1 been reported to in and sensitivity to hydrogen peroxide and Y. PubMed Scopus Google PubMed Scopus Google Scholar). phenotype been as a in NADPH for a thioredoxin-dependent in biosynthesis Biol. PubMed Scopus Google Scholar). H2O2s phenotype levels of NADPH to oxidative of the of the in this B. Mol. PubMed Scopus Google that H2O2s is a common phenotype for yeast with in enzymes of this on results of Biol. PubMed Scopus Google suggest that the by yeast strains lacking the cytosolic is to a of NADPH and that the can this In Biol. PubMed Scopus Google reported that in expression of cellular in yeast following to hydrogen peroxide suggest a major of carbon the of ZWF1 function conducted yeast with as a carbon source, a condition that expression of IDP2 Biol. 1993; PubMed Google 1994; PubMed Scopus Google Scholar). when IDP2 is expressed, of IDP2 or similar phenotypes and growth are by co-disruption of both we in to a for either ZWF1 or IDP2 to growth with fatty as a carbon source, the of both enzymes results in rapid loss of suggest that the of is oxidative damage to of hydrogen a major of peroxisomal and that significant levels of cytosolic NADPH are for of that in are to fatty as carbon sources the by peroxisomal β-oxidation as a both for and for carbon biosynthesis the (reviewed in and of the Saccharomyces and Scholar). Growth of yeast on oleate acid results in of and in of expression of peroxisomal the β-oxidation enzymes (reviewed in Refs. Scholar and and of the Saccharomyces and Scholar). in expression are also reported for peroxisomal PubMed Scopus Google the generated by the first step in of the and of peroxisomal NADP+-specific isocitrate dehydrogenase PubMed Scopus Google B. PubMed Scopus Google Scholar). PubMed Scopus Google and B. PubMed Scopus Google have essential and for the in β-oxidation of fatty acid and acid that require NADPH for of by In to these peroxisomal cytosolic PubMed Scopus Google and cytosolic IDP2, is by growth on are similar levels in with a of nonfermentable carbon sources Biol. 1993; PubMed Google or oleate of glucose-6-phosphate dehydrogenase (ZWF1) are with to carbon source Biol. PubMed Scopus Google PubMed Scopus Google as are levels of Biol. 1993; PubMed Google of IDP2 and with oleate as the carbon source. was conducted with that with yeast and IDP2 Biol. 1993; PubMed Google the strain on medium with or strains with oleate as the carbon mutant and ΔIDP3 mutant is shown of values for NADP+-specific isocitrate dehydrogenase Under these conditions, the not with the IDP3 the of the cellular in B. PubMed Scopus Google previously of growth with fatty as carbon sources for yeast strains containing disruptions ZWF1 Biol. PubMed Scopus Google Scholar). of the growth phenotypes by for strains with IDP3 disruptions PubMed Scopus Google B. PubMed Scopus Google the growth phenotype observed with of these disruptions was of strains containing disruptions of both IDP2 and ZWF1 to with fatty acid or as the carbon this growth phenotype ofΔIDP2ΔZWF1 strains by as following a of medium with to medium with oleate as the carbon source. in of with oleate for the the mutant strain containing both disruptions a rapid in viability when to oleate as carbon source. in for the with results following a of the to medium with carbon source the to loss of viability this Instead, the in viability for the strain is similar to the by a to oleate medium containing levels for values for loss of viability are for the ΔIDP2ΔZWF1 strain in medium with oleate and for the strain in medium with oleate and viability of yeast strains to medium with a fatty acid carbon source. and mutant yeast strains in medium with a fatty acid or carbon source as by the as with and these are to for of or values results suggest that transfer of the to medium with a fatty acid carbon source endogenous cellular that results in lethality. loss of viability is to that observed with the strain with of this as the to oleate as a carbon source. a of in strain is of levels of the of β-oxidation is by this this similar conducted a ΔIDP3 mutant of a of with a carbon source for this β-oxidation not require a peroxisomal source of NADPH PubMed Scopus Google B. PubMed Scopus Google Scholar). In when to medium with docosahexaenoate, a nonpermissive fatty acid carbon source, growth of strain that of the strain to carbon source strain a of with is loss of viability for the ΔIDP3 mutant strain in medium the of this In this mutant as in is to a for and to in the of NADPH generated by PubMed Scopus Google have of the of in a with docosahexaenoate, suggesting that is also of for the ΔIDP3 strain in medium with as carbon source to the of cellular ZWF1 and for removal of this to reduced of this by to these we growth of a strain containing disruptions and IDP3 in a of strain to medium a of in these not the of the In mutant strain a significant loss of viability following a to oleate of these results is that this loss of viability is to of in of β-oxidation when oleate is the of this loss of viability for the mutant strain when is the suggests that of to of to levels of we a previously to cellular in 1993; PubMed Scopus Google and yeast PubMed Scopus Google PubMed Scopus Google Scholar). This is to by to by and to by to form a with with a fatty acid for a to to this carbon source to significant in shown in of similar values are with significant in levels in strains with oleate and a in these levels in the ΔIDP3 strain with not with strains and growth to with that to loss of of cellular following to in of cellular strains for as in the for in medium with the fatty acid as carbon source. and of the to in for for as shown for the in associated to in to strains for as in the for in medium with the fatty acid as carbon source. and of the to in for for as shown for the in associated to in to in a Collectively, these results suggest that either ZWF1 or IDP2 is essential to the loss of viability that β-oxidation in yeast propose that the shared function is maintenance of high cytosolic redox ratios to function of NADPH-dependent enzymes involved in of or in of oxidative damage that and that these reactions are essential to function of this proposal is that IDP2, when expressed, of the reported previously for of ZWF1 PubMed Scopus Google that co-disruption of IDP2 these This was by growth of and mutant strains on with medium containing as the carbon source either expression of IDP2, or is to IDP2 expression Biol. 1993; PubMed Google Scholar). on growth with both carbon sources of of was by on a of results with are in on with as the carbon source, the H2O2s phenotypes are forΔZWF1 and ΔIDP2ΔZWF1 strains, the ΔIDP2 strain to that of the as a carbon source, both strain and the ΔIDP2 strain exhibit reduced growth to the strain with of that growth of the ΔIDP2ΔZWF1 results suggest a these cytosolic sources of NADPH for exogenous when both are this essential levels of ZWF1 are elevated Biol. PubMed Scopus Google and levels of IDP2 are not elevated not in to that in in levels of with functions cytosolic and Biol. PubMed Scopus Google phenotypes of yeast strains with disruptions in IDP2 and mutant yeast strains as containing either or as the carbon source, and the for or the strains with and with either or as the carbon source and the for or ΔZWF1 mutant strains are also reported to on we similar to by IDP2 on nonfermentable carbon as in the of ΔZWF1 mutant strains are on with as the carbon source, growth phenotypes are by of the mutant strains on with as the carbon source. biosynthesis on nonfermentable carbon sources not require ZWF1 IDP2. a in this that by is to the by in Biol. PubMed Scopus Google that is of NADPH for this growth this we that the of β-oxidation in can in the of major sources of cytosolic NADPH. of is damage of a of of of is to of the for of by the Biol. PubMed Scopus Google Scholar). propose that maintenance of a significant cytosolic of the reduced form of the cofactor is essential to function this and that the of the reducing equivalents to for enzymatic removal of a been and Biol. 1993; PubMed Google Biol. 1994; PubMed Google Scholar). on are encoding and that to have not been of the of a for NADPH in of the of endogenous of expression and of these enzymes is of significant Reducing equivalents in the form of NADPH are essential for many enzymatic steps involved in biosynthesis of cellular macromolecules. NADPH is also the essential cofactor for glutathione- and thioredoxin-dependent enzymes that constitute major cellular defenses against oxidative damage (reviewed in Refs. 1Wells W.W. Yang Y. Deits T.L. Gan Z.-R. Adv. Enzymol. Relat. Areas Mol. Biol. 1993; 66: 149-201PubMed Google Scholar and 2Halliwell B. Nutr. Rev. 1994; 52: 253-265Crossref PubMed Scopus (851) Google Scholar). In eucaryotic cells, the majority of these NADPH-dependent reactions occur in the cytosol. Availability of the reduced form of the cofactor requires maintenance of high steady-state cytosolic redox ratios for NADPH:NADP+ and values as high as ∼70:1 have been reported (3Stryer and Scholar). sources of NADPH are in In a Biol. PubMed Scopus Google we and phenotype analyses to the by the oxidative of the and by of NADP+-specific isocitrate that yeast are in of enzymatic sources of NADPH for containing disruptions In the growth phenotypes observed the of strains containing of genes encoding glucose-6-phosphate dehydrogenase (ZWF1) and cytosolic NADP+-specific isocitrate dehydrogenase to with fatty as a carbon source and the of ΔIDP2ΔZWF1 strains to In this we the fatty acid− growth phenotype by ΔIDP2ΔZWF1 yeast This phenotype is not observed for mutant strains containing a of ZWF1 or of IDP2, and the mutant strain containing both disruptions is of growth on as a carbon source Biol. PubMed Scopus Google Scholar). suggest that ZWF1 and have overlapping function in of β-oxidation of fatty a that is peroxisomal in (reviewed in Refs. Scholar and PubMed Scopus Google Scholar). of the yeast ZWF1 been reported to in and sensitivity to hydrogen peroxide and Y. PubMed Scopus Google PubMed Scopus Google Scholar). phenotype been as a in NADPH for a thioredoxin-dependent in biosynthesis Biol. PubMed Scopus Google Scholar). H2O2s phenotype levels of NADPH to oxidative of the of the in this B. Mol. PubMed Scopus Google that H2O2s is a common phenotype for yeast with in enzymes of this on results of Biol. PubMed Scopus Google suggest that the by yeast strains lacking the cytosolic is to a of NADPH and that the can this In Biol. PubMed Scopus Google reported that in expression of cellular in yeast following to hydrogen peroxide suggest a major of carbon the of ZWF1 function conducted yeast with as a carbon source, a condition that expression of IDP2 Biol. 1993; PubMed Google 1994; PubMed Scopus Google Scholar). when IDP2 is expressed, of IDP2 or similar phenotypes and growth are by co-disruption of both we in to a for either ZWF1 or IDP2 to growth with fatty as a carbon source, the of both enzymes results in rapid loss of suggest that the of is oxidative damage to of hydrogen a major of peroxisomal and that significant levels of cytosolic NADPH are for of that in are to fatty as carbon sources the by peroxisomal β-oxidation as a both for and for carbon biosynthesis the (reviewed in and of the Saccharomyces and Scholar). Growth of yeast on oleate acid results in of and in of expression of peroxisomal the β-oxidation enzymes (reviewed in Refs. Scholar and and of the Saccharomyces and Scholar). in expression are also reported for peroxisomal PubMed Scopus Google the generated by the first step in of the and of peroxisomal NADP+-specific isocitrate dehydrogenase PubMed Scopus Google B. PubMed Scopus Google Scholar). PubMed Scopus Google and B. PubMed Scopus Google have essential and for the in β-oxidation of fatty acid and acid that require NADPH for of by In to these peroxisomal cytosolic PubMed Scopus Google and cytosolic IDP2, is by growth on are similar levels in with a of nonfermentable carbon sources Biol. 1993; PubMed Google or oleate of glucose-6-phosphate dehydrogenase (ZWF1) are with to carbon source Biol. PubMed Scopus Google PubMed Scopus Google as are levels of Biol. 1993; PubMed Google previously of growth with fatty as carbon sources for yeast strains containing disruptions ZWF1 Biol. PubMed Scopus Google Scholar). of the growth phenotypes by for strains with IDP3 disruptions PubMed Scopus Google B. PubMed Scopus Google the growth phenotype observed with of these disruptions was of strains containing disruptions of both IDP2 and ZWF1 to with fatty acid or as the carbon this growth phenotype ofΔIDP2ΔZWF1 strains by as following a of medium with to medium with oleate as the carbon source. in of with oleate for the the mutant strain containing both disruptions a rapid in viability when to oleate as carbon source. in for the with results following a of the to medium with carbon source the to loss of viability this Instead, the in viability for the strain is similar to the by a to oleate medium containing levels for values for loss of viability are for the ΔIDP2ΔZWF1 strain in medium with oleate and for the strain in medium with oleate and viability of yeast strains to medium with a fatty acid carbon source. and mutant yeast strains in medium with a fatty acid or carbon source as by the as with and these are to for of or values results suggest that transfer of the to medium with a fatty acid carbon source endogenous cellular that results in lethality. loss of viability is to that observed with the strain with of this as the to oleate as a carbon source. a of in strain is of levels of the of β-oxidation is by this this similar conducted a ΔIDP3 mutant of a of with a carbon source for this β-oxidation not require a peroxisomal source of NADPH PubMed Scopus Google B. PubMed Scopus Google Scholar). In when to medium with docosahexaenoate, a nonpermissive fatty acid carbon source, growth of strain that of the strain to carbon source strain a of with is loss of viability for the ΔIDP3 mutant strain in medium the of this In this mutant as in is to a for and to in the of NADPH generated by PubMed Scopus Google have of the of in a with docosahexaenoate, suggesting that is also of for the ΔIDP3 strain in medium with as carbon source to the of cellular ZWF1 and for removal of this to reduced of this by to these we growth of a strain containing disruptions and IDP3 in a of strain to medium a of in these not the of the In mutant strain a significant loss of viability following a to oleate of these results is that this loss of viability is to of in of β-oxidation when oleate is the of this loss of viability for the mutant strain when is the suggests that of to of to levels of we a previously to cellular in 1993; PubMed Scopus Google and yeast PubMed Scopus Google PubMed Scopus Google Scholar). This is to by to by and to by to form a with with a fatty acid for a to to this carbon source to significant in shown in of similar values are with significant in levels in strains with oleate and a in these levels in the ΔIDP3 strain with not with strains and growth to with that to loss of of cellular following to in of cellular strains for as in the for in medium with the fatty acid as carbon source. and of the to in for for as shown for the in associated to in to strains for as in the for in medium with the fatty acid as carbon source. and of the to in for for as shown for the in associated to in to in a Collectively, these results suggest that either ZWF1 or IDP2 is essential to the loss of viability that β-oxidation in yeast propose that the shared function is maintenance of high cytosolic redox ratios to function of NADPH-dependent enzymes involved in of or in of oxidative damage that and that these reactions are essential to function of this proposal is that IDP2, when expressed, of the reported previously for of ZWF1 PubMed Scopus Google that co-disruption of IDP2 these This was by growth of and mutant strains on with medium containing as the carbon source either expression of IDP2, or is to IDP2 expression Biol. 1993; PubMed Google Scholar). on growth with both carbon sources of of was by on a of results with are in on with as the carbon source, the H2O2s phenotypes are forΔZWF1 and ΔIDP2ΔZWF1 strains, the ΔIDP2 strain to that of the as a carbon source, both strain and the ΔIDP2 strain exhibit reduced growth to the strain with of that growth of the ΔIDP2ΔZWF1 results suggest a these cytosolic sources of NADPH for exogenous when both are this essential levels of ZWF1 are elevated Biol. PubMed Scopus Google and levels of IDP2 are not elevated not in to that in in levels of with functions cytosolic and Biol. PubMed Scopus Google phenotypes of yeast strains with disruptions in IDP2 and mutant yeast strains as containing either or as the carbon source, and the for or the strains with and with either or as the carbon source and the for or ΔZWF1 mutant strains are also reported to on we similar to by IDP2 on nonfermentable carbon as in the of ΔZWF1 mutant strains are on with as the carbon source, growth phenotypes are by of the mutant strains on with as the carbon source. biosynthesis on nonfermentable carbon sources not require ZWF1 IDP2. a in this that by is to the by in Biol. PubMed Scopus Google that is of NADPH for this growth this we that the of β-oxidation in can in the of major sources of cytosolic NADPH. of is damage of a of of of is to of the for of by the Biol. PubMed Scopus Google Scholar). propose that maintenance of a significant cytosolic of the reduced form of the cofactor is essential to function this and that the of the reducing equivalents to for enzymatic removal of a been and Biol. 1993; PubMed Google Biol. 1994; PubMed Google Scholar). on are encoding and that to have not been of the of a for NADPH in of the of endogenous of expression and of these enzymes is of significant are to fatty as carbon sources the by peroxisomal β-oxidation as a both for and for carbon biosynthesis the (reviewed in and of the Saccharomyces and Scholar). Growth of yeast on oleate acid results in of and in of expression of peroxisomal the β-oxidation enzymes (reviewed in Refs. Scholar and and of the Saccharomyces and Scholar). in expression are also reported for peroxisomal PubMed Scopus Google the generated by the first step in of the and of peroxisomal NADP+-specific isocitrate dehydrogenase PubMed Scopus Google B. PubMed Scopus Google Scholar). PubMed Scopus Google and B. PubMed Scopus Google have essential and for the in β-oxidation of fatty acid and acid that require NADPH for of by In to these peroxisomal cytosolic PubMed Scopus Google and cytosolic IDP2, is by growth on are similar levels in with a of nonfermentable carbon sources Biol. 1993; PubMed Google or oleate of glucose-6-phosphate dehydrogenase (ZWF1) are with to carbon source Biol. PubMed Scopus Google PubMed Scopus Google as are levels of Biol. 1993; PubMed Google previously of growth with fatty as carbon sources for yeast strains containing disruptions ZWF1 Biol. PubMed Scopus Google Scholar). of the growth phenotypes by for strains with IDP3 disruptions PubMed Scopus Google B. PubMed Scopus Google the growth phenotype observed with of these disruptions was of strains containing disruptions of both IDP2 and ZWF1 to with fatty acid or as the carbon source. this growth phenotype ofΔIDP2ΔZWF1 strains by as following a of medium with to medium with oleate as the carbon source. in of with oleate for the the mutant strain containing both disruptions a rapid in viability when to oleate as carbon source. in for the with results following a of the to medium with carbon source the to loss of viability this Instead, the in viability for the strain is similar to the by a to oleate medium containing levels for values for loss of viability are for the ΔIDP2ΔZWF1 strain in medium with oleate and for the strain in medium with oleate results suggest that transfer of the to medium with a fatty acid carbon source endogenous cellular that results in lethality. loss of viability is to that observed with the strain with of this as the to oleate as a carbon source. a of in strain is of levels of the of β-oxidation is by this this similar conducted a ΔIDP3 mutant of a of with a carbon source for this β-oxidation not require a peroxisomal source of NADPH PubMed Scopus Google B. PubMed Scopus Google Scholar). In when to medium with docosahexaenoate, a nonpermissive fatty acid carbon source, growth of strain that of the strain to carbon source strain a of with is loss of viability for the ΔIDP3 mutant strain in medium the of this In this mutant as in is to a for and to in the of NADPH generated by PubMed Scopus Google have of the of in a with docosahexaenoate, suggesting that is also of for the ΔIDP3 strain in medium with as carbon source to the of cellular ZWF1 and for removal of this to reduced of this by to these we growth of a strain containing disruptions and IDP3 in a of strain to medium a of in these not the of the In mutant strain a significant loss of viability following a to oleate of these results is that this loss of viability is to of in of β-oxidation when oleate is the of this loss of viability for the mutant strain when is the suggests that of to of to levels of we a previously to cellular in 1993; PubMed Scopus Google and yeast PubMed Scopus Google PubMed Scopus Google Scholar). This is to by to by and to by to form a with with a fatty acid for a to to this carbon source to significant in shown in of similar values are with significant in levels in strains with oleate and a in these levels in the ΔIDP3 strain with not with strains and growth to with that to loss of Collectively, these results suggest that either ZWF1 or IDP2 is essential to the loss of viability that β-oxidation in yeast propose that the shared function is maintenance of high cytosolic redox ratios to function of NADPH-dependent enzymes involved in of or in of oxidative damage that and that these reactions are essential to function of this proposal is that IDP2, when expressed, of the reported previously for of ZWF1 PubMed Scopus Google that co-disruption of IDP2 these This was by growth of and mutant strains on with medium containing as the carbon source either expression of IDP2, or is to IDP2 expression Biol. 1993; PubMed Google Scholar). on growth with both carbon sources of of was by on a of results with are in on with as the carbon source, the H2O2s phenotypes are forΔZWF1 and ΔIDP2ΔZWF1 strains, the ΔIDP2 strain to that of the as a carbon source, both strain and the ΔIDP2 strain exhibit reduced growth to the strain with of that growth of the ΔIDP2ΔZWF1 results suggest a these cytosolic sources of NADPH for exogenous when both are this essential levels of ZWF1 are elevated Biol. PubMed Scopus Google and levels of IDP2 are not elevated not in to that in in levels of with functions cytosolic and Biol. PubMed Scopus Google Scholar). ΔZWF1 mutant strains are also reported to on we similar to by IDP2 on nonfermentable carbon as in the of ΔZWF1 mutant strains are on with as the carbon source, growth phenotypes are by of the mutant strains on with as the carbon source. biosynthesis on nonfermentable carbon sources not require ZWF1 IDP2. a in this that by is to the by in Biol. PubMed Scopus Google that is of NADPH for this growth In this we that the of β-oxidation in can in the of major sources of cytosolic NADPH. of is damage of a of of of is to of the for of by the Biol. PubMed Scopus Google Scholar). propose that maintenance of a significant cytosolic of the reduced form of the cofactor is essential to function this and that the of the reducing equivalents to for enzymatic removal of a been and Biol. 1993; PubMed Google Biol. 1994; PubMed Google Scholar). on are encoding and that to have not been of the of a for NADPH in of the of endogenous of expression and of these enzymes is of significant for and for with