硫化氢与mTORC1途径相互作用调控细胞氧化还原平衡与衰老的分子机制

气体信号分子硫化氢在调控从酵母到人类细胞的氧化还原平衡和衰老中具有重要作用。我们初步的研究工作发现硫化氢可以调控细胞代谢、胁迫应答以及衰老的关键途径mTORC1途径，同时mTORC1途径也会影响內源硫化氢的生成。然而对于二者相互作用的分子机制和生理意义还需要进一步研究。因此本项目将首先验证硫化氢对mTORC1途径的调控作用以及mTORC1是否介导硫化氢的生理效应，同时我们将着重研究硫化氢对mTORC1途径直接作用的修饰位点，从而阐明硫化氢调控 mTORC1的确切机制。最后我们将探索mTORC1调控內源硫化氢生成的机制以及硫化氢和mTORC1相互作用的生理意义。本项目研究将有助于深入了解mTORC1途径的调控机理，硫化氢的作用机制，以及二者相互作用对细胞氧化还原平衡和衰老调控的影响，为开发相应药物干预衰老和衰老相关疾病提供重要参考。

As a gaseous signaling molecular, hydrogen sulfide plays an important role in redox balance and aging from yeast to human cells. Our preliminary studies suggest that hydrogen sulfide may regulate mTORC1 pathway which is the master regulator for cellular metabolism, stress responses and aging and mTORC1 may also regulate the production of endogenous hydrogen sulfide. However, the molecular mechanism and physiological significance of their crosstalk require further study. This proposed study will firstly verify the regulation of mTORC1 by hydrogen sulfide and the requirement of mTORC1 for the physiological effects of hydrogen sulfide. We will put emphasis on the identification of targets in mTORC1 modified by hydrogen sulfide to elucidate the mechanism. We will also study how mTORC1 controls the production of endogenous hydrogen sulfide. Our study will help us to further understand the regulation of mTORC1, the mechanism of hydrogen sulfide action and the effects of their crosstalk in redox balance and aging and finally benefits the development of drugs to intervene aging and age-related diseases.