RRC ID 49493
著者 Enya S, Yamamoto C, Mizuno H, Esaki T, Lin HK, Iga M, Morohashi K, Hirano Y, Kataoka H, Masujima T, Shimada-Niwa Y, Niwa R.
タイトル Dual Roles of Glutathione in Ecdysone Biosynthesis and Antioxidant Function During Larval Development in Drosophila.
ジャーナル Genetics
Abstract Ecdysteroids, including the biologically active hormone 20-hydroxyecdysone (20E), play essential roles in controlling many developmental and physiological events in insects. Ecdysteroid biosynthesis is achieved by a series of specialized enzymes encoded by the Halloween genes. Recently, a new class of Halloween gene, noppera-bo (nobo), encoding a glutathione S-transferase (GST) in dipteran and lepidopteran species, has been identified and characterized. GSTs are well known to conjugate substrates with the reduced form of glutathione (GSH), a bioactive tripeptide composed of glutamate, cysteine, and glycine. We hypothesized that GSH itself is required for ecdysteroid biosynthesis. However, the role of GSH in steroid hormone biosynthesis has not been examined in any organisms. Here, we report phenotypic analysis of a complete loss-of-function mutant in the γ-glutamylcysteine synthetase catalytic subunit (Gclc) gene in the fruit fly Drosophila melanogasterGclc encodes the evolutionarily conserved catalytic component of the enzyme that conjugates glutamate and cysteine in the GSH biosynthesis pathway. Complete Gclc loss-of-function leads to drastic GSH deficiency in the larval body fluid. Gclc mutant animals show a larval-arrest phenotype. Ecdysteroid titer in Gclc mutant larvae decreases, and the larval-arrest phenotype is rescued by oral administration of 20E or cholesterol. Moreover, Gclc mutant animals exhibit abnormal lipid deposition in the prothoracic gland, a steroidogenic organ during larval development. All of these phenotypes are reminiscent to nobo loss-of-function animals. On the other hand, Gclc mutant larvae also exhibit a significant reduction in antioxidant capacity. Consistent with this phenotype, Gclc mutant larvae are more sensitive to oxidative stress response as compared to wild-type. Nevertheless, the ecdysteroid biosynthesis defect in Gclc mutant animals is not associated with loss of antioxidant function. Our data raise the unexpected hypothesis that a primary role of GSH in early D. melanogaster larval development is ecdysteroid biosynthesis, independent from the antioxidant role of GSH.
巻・号 207(4)
ページ 1519-1532
公開日 2017-12-1
DOI 10.1534/genetics.117.300391
PII genetics.117.300391
PMID 29021278
PMC PMC5714463
MeSH Animals Antioxidants / metabolism Catalytic Domain / genetics Cholesterol / pharmacology Drosophila Proteins / genetics Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Ecdysone / biosynthesis Ecdysone / genetics* Embryonic Development / genetics Glutamate-Cysteine Ligase / genetics* Glutathione / metabolism Glutathione Transferase / genetics* Larva / genetics Larva / growth & development Mutation
IF 4.015
引用数 10
リソース情報
ショウジョウバエ TBX-0002 CAS-0001 pBFv-U6.2