LAUSR

Growth and development are affected by cellular redox homeostasis which is modulated partly by NADPH status. Both glucose 6-phosphate dehydrogenase (G6PD) and isocitrate dehydrogenase1 (IDH1) are responsible for the regeneration of NADPH in cells. To investigate the role of IDH1 in G6PD deficiency, G6PD/IDH1 double deficient C. elegans were produced. The G6PD/IDH1 double-deficient C. elegans showed shrinkage of body size, growth retardation and impaired molting. These defects were not observed in either G6PD or IDH1 deficient C. elegans. Global metabolomic analyses were used to examine metabolic pathways in G6PD/IDH1 double deficient worms. Principal component analysis showed a distinct metabolomic profile of G6PD/IDH1 double deficient worms. Further metabolomic analysis revealed that the biosynthesis of many amino acids was significantly impaired, particularly those NADPH-dependent amino acids. The reduced amino acid levels can affect protein synthesis as corroborated by the absence of NAS-37 expression during the molting process leading to growth retardation and molting defects. These defects in G6PD/IDH1 double deficient C. elegans suggest that both enzymes are important in the regeneration of NADPH and maintenance of cellular redox homeostasis for proper cellular function.