线粒体内质网结构偶联（MAM）是重要的细胞器互作模式，可影响多种细胞生物学过程，并与肝脏疾病发生进展密切相关。我们前期研究发现肝癌细胞中MAM形成减少，并与患者较差预后相关。通过质谱筛选发现小GTPase Rab32在肝癌MAM定位显著减少，进一步在肝癌细胞中下调Rab32，发现MAM形成减少。然而Rab32在肝癌MAM结构形成和交互功能中的作用机制尚待系统阐明。以往文献报道，MAM可调控线粒体钙稳态和代谢重编程。据此我们提出假说：肝癌细胞中Rab32作为结构组成型蛋白定位减少，调控MAM形成减少，进一步通过下调线粒体钙、上调糖酵解水平，最终促进肝癌细胞生长。本项目拟利用细胞、动物模型以及临床样本，系统研究：肝癌MAM形成减少对肝癌细胞生长作用，以及Rab32调控肝癌MAM结构形成和功能的作用及机制。本项目的开展有助于揭示肝癌MAM形成和功能的调控机制，同时也可为肝癌防治提供新的理论认识。

Mitochondria-associated endoplasmic reticulum membranes (MAM) are an important organelle interaction mode that can affect a variety of cellular biological processes and are closely related to the development of the liver disease. Our previous study found that the formation of MAM in HCC cells was reduced and related to the poor prognosis. Screening by mass spectrometry revealed that the localization of small GTPase Rab32 in MAM of HCC was significantly reduced, Further down-regulation of Rab32 in HCC cells revealed that MAM formation was reduced. However, the mechanism of Rab32 regulates the MAM formation and functions in HCC cells remains to be systematically elucidated. Previous literature reports that MAM can regulate mitochondrial calcium homeostasis and metabolic reprogramming. Based on this, we propose a hypothesis that the localization of Rab32 as a structural constitutive protein in HCC cells decreased, reduced the formation of MAM, and further down-regulates mitochondrial calcium intake and up-regulates glycolysis levels, ultimately promoted the growth of HCC cells. This project intends to use cell lines, animal models, and clinical samples to systematically study: the effect of reduced MAM formation on the growth of HCC cells, and the role and mechanism of Rab32 in regulating the formation and function of MAM structure in HCC. The implementation of this project can further understand the interactive function and regulation mechanism of MAM in HCC cells, and also provide new theoretical knowledge for the prevention and treatment of HCC.