Royal jelly attenuates metabolic defects in a Drosophila mutant with elevated TORC1 activity.

Yang Cheng,Yue Hao,Congjing Feng,Jiadong Cai,Yuanyuan Fu,Youheng Wei

doi:10.1242/bio.054999

Abstract

ABSTRACTTarget of rapamycin complex 1 (TORC1) is a master regulator of cell metabolism, and its dysregulation has been linked to an array of pathologies, including cancer and age-related diseases. Nprl3, a component of GTPase-activating protein towards Rags complex 1 (GATOR1), inhibits TORC1 activity under nutrient scarcity status. The nprl3 mutant exhibits some metabolic defects due to hyper TORC1 activity in Drosophila. Royal jelly (RJ) is a honeybee-secreted product and plays an essential role in caste differentiation that requires TORC1 activity. RJ is also used as a health-benefit food for its potential roles on antioxidant and anti-aging. In this study, nprl3-mutant flies were used to measure the effect of RJ on metabolic modulation. Interestingly, RJ feeding significantly increased survival and decreased TORC1 activity in the nprl3 mutant. RJ feeding also ameliorated the abnormal reactive oxygen species (ROS) levels and energy status in the nprl3 mutant. The proteins in RJ were characterized to be the essential components in increasing nprl3 mutant viability. These findings suggest that RJ modulates some metabolic defects associated with elevated TORC1 activity and that the nprl3-mutant fly might be a useful tool for investigating the bioactive components of RJ in vivo.

Highlights

Target of rapamycin complex 1 (TORC1) is a master regulator that mediates nutrient status and metabolism
Royal jelly (RJ) improves the survival of nprl3-mutant flies The nprl3-mutant flies are semi-lethal and display multiple agerelated pathologies and metabolic defects, owing to elevated TORC1 activity (Wei et al, 2016)
reactive oxygen species (ROS) is generated as a byproduct, especially in damaged mitochondria (Zorov et al, 2014)

Summary

Introduction

Target of rapamycin complex 1 (TORC1) is a master regulator that mediates nutrient status and metabolism. It promotes protein synthesis and cell growth by phosphorylating downstream effectors, such as p70 S6 kinase (S6K) and eIF-4E binding protein (4E-BP) (Bar-Peled and Sabatini, 2014; Kim and Guan, 2019). The nprl3mutant flies exhibit increased TORC1 activity and a variety of related phenotypes, such as semi-lethality, short lifespan, decreased motility, and some metabolic defects (Wei et al, 2016)

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Results

Conclusion