Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans

Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

G6PD is highly conserved from bacteria to human (Figure 1) . Previous studies have shown that G6PD deletion does not affect the viability of E. coli. 29 Likewise, G6PD-null S. cerevisiae grows normally, except for the nutritional requirement of organic sulfur. 30 Mild G6PD deficiency (40% of normal activity) moderately affects cardiac function in a mouse model. 31 In contrast, severe G6PD deficiency leads to 32 Currently, the lack of a workable G6PD-deficient animal model is the major obstacle to reveal the role of G6PD in organismal level. In the present study, G6PD-deficient C. elegans is established by RNAi knockdown as a viable and workable model system. Upon G6PD knockdown, C. elegans demonstrates significant reduction of G6PD expression and catalytic activity (Figure 2) , which are consistent with reduced G6PD status in G6PD-knockdown cells. 13 G6PD deficiency is associated with embryonic lethality in animals. Indeed, the most dramatic finding in this study is the extremely low hatching of eggs derived from G6PD-knockdown C. elegans (Figure 4c ). This result is supported by previous reports in mice 32 and C. elegans from a large-scale RNAi screen. 24 Consistently, the low hatching of eggs from G6PD-knockdown C. elegans provides strong evidence to the notion that G6PD is indispensable for embryonic survival in C. elegans. However, the underlying mechanism on how G6PD status affects embryonic survival is largely unknown.