Identification of a sterol mutant of Neurospora crassa deficient in A14,15-reductase activity

Ellis, S. W.; Rose, Malcolm E.; Grindle, M.

doi:10.1099/00221287-137-11-2627

Cited by 18 publications

(6 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, these results allowed us to conclude that the e r g 3 null mutants lack ergosterol and accumulate ignosterol just as reported by Ellis et al (1991) for the original erg-3 mutant.…”

Section: Induction Of Rip In Erg-3supporting

confidence: 81%

“…The erg-3 mutant is unable to synthesize the wildtype sterol ergosterol ; instead it accumulates precursor sterols that remain unsaturated in the A1'.15 bond that forms following the C-14 demethylation step in the ergosterol biosynthetic pathway. This led to the suggestion that erg-3 might encode the enzyme A14,15-reductase (Ellis et al, 1991). Two additional phenotypes were found f o r the erg-3 mutant in our laboratory that were related to altered sensitivities to pisatin, an isoflavonoid phytoalexin of pea, and to a-tomatine, a steroidal glycoside phytoanticipin of tomato (Papavinasasundaram 6: Kasbekar, 1993;Sengupta et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The erg-3 (sterol Δ14,15-reductase) gene of Neurospora crassa: generation of null mutants by repeat-induced point mutation and complementation by proteins chimeric for human lamin B receptor sequences

Prakash¹,

Sengupta²,

Aparna³

et al. 1999

Microbiology

View full text Add to dashboard Cite

Null mutations were generated in the erg-3 gene of Neurospora crassa by repeat-induced point mutation (RIP). The mutants were viable, lacked ergosterol, were resistant to the steroidal glycoside a-tomatine and were sensitive to the phytoalexins pisatin and biochanin A. RIP was frequently associated with silencing of the hph gene located adjacent to the duplicated erg-3 sequence. The silencing of hph was reversible in the two cases examined and appeared to be due to the spread of cytosine methylation associated with RIP. The erg-3 mutant could be complemented by transformation with recombinant genes that encode proteins chimeric for amino acid sequences from the transmembrane (TM) domain of human lamin B receptor (LBR). This indicates that the LBR T M domain possesses A14n15-red~cta~e activity.

show abstract

Section: Induction Of Rip In Erg-3supporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

The erg-3 (sterol Δ14,15-reductase) gene of Neurospora crassa: generation of null mutants by repeat-induced point mutation and complementation by proteins chimeric for human lamin B receptor sequences

Prakash¹,

Sengupta²,

Aparna³

et al. 1999

Microbiology

View full text Add to dashboard Cite

show abstract

“…Argininic acid, α-keto-δ-guanidinovaleric acid, and γ-guanidinobutyric acid are members of arginine metabolism (as well as other uremic toxins) and thus are highly dependent on fully-functioning mitochondria and are key players in arginine metabolism. Enzymes such as amidinotransferase, d -amino-acid oxidase, and N -acetyl- l -glutamate synthase, which are described as being involved in the synthesis or metabolism of these acids, are also localized in mitochondria [31,32,33]. Hippuric acid is a product of phenols and phenylalanine metabolism and can be produced by mitochondrial glycine N-benzoyltransferase [34].…”

Section: Mitochondria As a Source Of Damaging And Toxic Moleculesmentioning

confidence: 99%

Mitochondria as a Source and a Target for Uremic Toxins

Popkov

Silachev

Zalevsky

et al. 2019

IJMS

View full text Add to dashboard Cite

Elucidation of molecular and cellular mechanisms of the uremic syndrome is a very challenging task. More than 130 substances are now considered to be “uremic toxins” and represent a very diverse group of molecules. The toxicity of these molecules affects many cellular processes, and expectably, some of them are able to disrupt mitochondrial functioning. However, mitochondria can be the source of uremic toxins as well, as the mitochondrion can be the site of complete synthesis of the toxin, whereas in some scenarios only some enzymes of the pathway of toxin synthesis are localized here. In this review, we discuss the role of mitochondria as both the target and source of pathological processes and toxic compounds during uremia. Our analysis revealed about 30 toxins closely related to mitochondria. Moreover, since mitochondria are key regulators of cellular redox homeostasis, their functioning might directly affect the production of uremic toxins, especially those that are products of oxidation or peroxidation of cellular components, such as aldehydes, advanced glycation end-products, advanced lipoxidation end-products, and reactive carbonyl species. Additionally, as a number of metabolic products can be degraded in the mitochondria, mitochondrial dysfunction would therefore be expected to cause accumulation of such toxins in the organism. Alternatively, many uremic toxins (both made with the participation of mitochondria, and originated from other sources including exogenous) are damaging to mitochondrial components, especially respiratory complexes. As a result, a positive feedback loop emerges, leading to the amplification of the accumulation of uremic solutes. Therefore, uremia leads to the appearance of mitochondria-damaging compounds, and consecutive mitochondrial damage causes a further rise of uremic toxins, whose synthesis is associated with mitochondria. All this makes mitochondrion an important player in the pathogenesis of uremia and draws attention to the possibility of reducing the pathological consequences of uremia by protecting mitochondria and reducing their role in the production of uremic toxins.

show abstract

“…We tested this prediction using the erg mutants of N. crassa. The Neurospora erg mutations alter the composition of membrane sterols and confer nystatin resistance (Grindle, 1973) by blocking specific steps in ergosterol biosynthesis : erg1 mutations affect A',' isomerization (Grindle & Farrow, 1978), erg3 mutations affect the Al4.I5 reductase activity (Ellis et al, 1991). We found that, compared to the wild-type, the erg1 and erg3 mutants were much more sensitive to growth inhibition on medium containing 40 pg pisatin ml-' ( Table 4).…”

Section: Sterol Mutants Of N Crassa Are Pisatin-sensitivementioning

confidence: 82%

Pisatin resistance in Dictyostelium discoideum and Neurospora crassa: comparison of mutant phenotypes

Papavinasasundaram

Kasbekar

1993

Journal of General Microbiology

View full text Add to dashboard Cite

~ ~~~The pea phytoalexin pisatin, at its inhibitory concentration, was shown to have two distinct inhibitory effects on amoebae of the cellular slime mould Dictyostelium discoideum. One effect was cytolytic and was demonstrable even in non-growing cells whereas the second effect was observed only under conditions favourable to growth. Pretreatment with a sublethal concentration of pisatin induced the amoebae to acquire resistance to both these effects. Mutations in nysC that alter membrane sterols and confer resistance to the polyene antibiotics nystatin and pimaricin blocked resistance to the growth-associated inhibitory effect but did not affect acquisition of resistance to the cytolytic effect. The nysB sunD double mutant HK412 displayed a partially constitutive resistance to the cytolytic effect but, like the nysC mutants, was blocked in the acquisition of resistance to the growth-associated inhibitory effect. Pisatin-treated cells incubated in pisatin-free medium lost their ability to grow on pisatincontaining medium much more rapidly than they lost resistance to the cytolytic effect of pisatin. These results suggest that the induction of pisatin resistance may involve the turning-on of independent resistance mechanisms against the two inhibitory effects of pisatin. This could account for our inability to isolate pisatin-resistant mutants in a single step. The Neurospora crassa erg1 and erg3 mutants that have altered membrane sterols and are nystatin resistant displayed sensitivity to pisatin. The pisatin-sensitivity phenotype of the erg mutants was used in selections to identify complementing plasmids from an ordered Neurospora genomic library. The association of pisatin sensitivity with membrane sterol alterations in both D. discoideum and N. crassa supports the hypothesis that mechanisms underlying nondegradative pisatin resistance are evolutionarily conserved.

show abstract

Identification of a sterol mutant of Neurospora crassa deficient in A14,15-reductase activity

Cited by 18 publications

References 18 publications

The erg-3 (sterol Δ14,15-reductase) gene of Neurospora crassa: generation of null mutants by repeat-induced point mutation and complementation by proteins chimeric for human lamin B receptor sequences

The erg-3 (sterol Δ14,15-reductase) gene of Neurospora crassa: generation of null mutants by repeat-induced point mutation and complementation by proteins chimeric for human lamin B receptor sequences

Mitochondria as a Source and a Target for Uremic Toxins

Pisatin resistance in Dictyostelium discoideum and Neurospora crassa: comparison of mutant phenotypes

Contact Info

Product

Resources

About