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bioRxiv · 10.1101/2024.12.02.626170

Glucose-6-phosphatase is required for sperm energy metabolism, motility and fertility in Drosophila

Hedjazi, S.·Miyamoto, T.·Ahn, J.-E.·Sitcheran, R.·Amrein, H.
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Abstract

Glucose-6-Phosphatase (G6Pase), a key enzyme in gluconeogenesis and glycogenolysis in the mammalian liver and kidney, converts glucose-6-phosphate to glucose for maintaining systemic blood glucose homeostasis during nutrient deprivation. However, its function has remained elusive in insects, which have no need for G6Pase in sugar homeostasis since they convert glucose-6-phosphate to trehalose, their main circulating sugar, via trehalose phosphate synthase (TPS1). In this study we identify an unexpected and essential requirement for G6Pase in Drosophila male fertility, specifically to produce motile sperm. In G6P mutant males, spermatogenesis and spermiogenesis appear to proceed normally, leading to the production and transfer of mature sperm. However, once inside the female reproductive tract, G6P mutant sperm exhibit severely reduced tail beat frequency and only rarely enter an egg. Moreover, when compared to wild type sperm, G6P-deficient sperm are depleted more rapidly from the spermatheca and seminal receptacle, the female sperm storage organs. Immunohistochemical analyses show that G6P mutant spermatocytes present with an enlarged and stressed endoplasmic reticulum (ER) and a diminished Golgi apparatus. Additionally, the acrosome, a Golgi derived organelle that is critical for sperm capacitation, exhibits diminished expression of the transmembrane protein SNEAKY, which is essential to breakdown the sperm plasma membrane after fertilization. Metabolic analyses show impairment of both basal and compensatory glycolysis, as well as ATP production, in testes of G6P mutant males. Taken together, our investigations unveil a novel and crucial function for G6Pase in male fertility, highlighting its importance in regulating energy homeostasis in reproductive tissues.

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Hedjazi, S., Miyamoto, T., Ahn, J.-E., Sitcheran, R., Amrein, H.. 2024-12-02. Glucose-6-phosphatase is required for sperm energy metabolism, motility and fertility in Drosophila. https://doi.org/10.1101/2024.12.02.626170

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