多种细胞器参与调控脂滴生成、形态维持以及代谢的相关机制已逐步被揭示和阐述，但脂滴直接调控其他细胞器形态和功能的相关研究却鲜有报道。申请人在酿酒酵母菌中的初步研究显示：1）脂滴缺失突变体中液泡呈明显碎片化状态；2）脂滴中性脂构成影响液泡表面蛋白的降解；3）脂滴表面附着有液泡蛋白且其丰度受中性脂构成影响；据此推测脂滴可能参与调控液泡的形态及相关功能。此外，脂滴也能直接影响细胞自噬进程，且液泡又是细胞自噬的最终完成场所。基于上述发现，本立项申请拟探索：1）脂滴对液泡形态与功能的具体影响；2）脂滴对液泡生理的调控与细胞自噬的相关性与因果关系；3）脂滴影响液泡生理的潜在作用机制。通过本研究将增进我们对脂滴功能新的认知，加深对液泡生理与细胞自噬调控机制相关性的理解，并有望帮助阐述部分病原真菌的致病侵染机制以及为人类脂代谢相关疾病探寻新的治疗靶点提供一定的理论基础。

The mechanisms of multiple organelles involved in regulating the formation, morphological maintenance and metabolism of lipid droplets have been gradually revealed, but lipid droplets involved in regulating the morphology and functions of other organelles has been rarely reported. Our preliminary studies in Saccharomyces cerevisiae, showed that: 1) Vacuoles were fragmented in cells without lipid droplets; 2) Neutral lipids in droplets affected the degradation of a vacuolar surface protein; and 3) Vacuolar surface proteins have been found on the lipid droplets, and the protein abundance was significantly affected by neutral lipids. Based on these results, we speculated that lipid droplets may involved in regulating the morphology and functions of vacuoles. It has also been reported that lipid droplets and their component triglycerides and steryl esters can regulate autophagy, as well as the final step of autophagy is fusion with vacuoles for degradation. In this application, we are intended to answer three questions in budding yeast: 1) Can lipid droplets affect the morphology and function of vacuoles? 2) What is the correlation and causality between the autophagy process and the regulation of lipid droplet in vacuolar physiology? 3) What is the molecular mechanism of lipid droplets in regulating the physiology of vacuoles? This study will not only improve our knowledge about lipid droplets, but also may deepen our understanding of the correlation between autophagy process and vacuolar physiology. These findings hopefully further help us elucidate the pathogenic mechanism of pathogenic fungi as well as provide a theoretical basis for new therapeutic targets of human lipid metabolism diseases.