BLOS1是蛋白复合体BLOC1和BORC的共有亚基，这两个蛋白复合体分别参与溶酶体相关细胞器的形成和溶酶体的亚细胞定位；同时，BLOS1可参与线粒体呼吸、能量和物质代谢，但尚不清楚其作用的分子机制。我们发现编码BLOS1的基因突变，导致斑马鱼幼鱼出现不依赖于BLOC1和BORC功能的肝肿大和肝细胞坏死，肝细胞内出现线粒体膨大、结构异常、油滴积累。在此基础上，本项目拟利用细胞、分子、蛋白质组学等技术，深入开展以下研究：1）鉴定斑马鱼肝细胞内与BLOS1相互作用的线粒体靶蛋白；2）BLOS1对肝脏线粒体靶蛋白的乙酰化作用和分子机制；3）BLOS1对肝细胞能量代谢的调控与机制；4）BLOS1对肝细胞ROS形成的调控与机制；5）BLOS1对肝细胞内脂肪酸代谢的调控与机制。本项目的获准与顺利实施，将揭示斑马鱼BLOS1在调控肝细胞命运和肝脏功能中的作用与分子机制，为肝脏相关疾病诊治提供理论基础。

BLOS1 is a common subunit of protein complexes BLOC1 and BORC, which are involved in the formation of lysosome-related organelles and subcellular localization of lysosomes, respectively. In addition, BLOS1 is reported to play roles in mitochondrial respiration, energy and substance metabolisms; however, molecular mechanisms of BLOS1 functions remain unclear. We found that mutation of the gene encoding zebrafish BLOS1 led to hepatomegaly and necrosis of liver cells in a BLOC1- and BORC- independent manner, and mitochondrial swelling and abnormal structure as well as and oil accumulation appeared in liver cells. Based on these findings, the project intends to carry out the following researches by using cellular, molecular and proteomic approaches: 1) identification of target proteins interacting with BLOS1 in the mitochondrial of zebrafish liver cells; 2) acetylation and molecular mechanisms of target proteins by BLOS1 in mitochondrial of liver cells; 3) regulation and mechanisms of energy metabolism by BLOS1 in liver cells; 4) regulation and mechanisms of ROS generation by BLOS1 in liver cells; 5) regulation and mechanisms of fatty acid metabolism by BLOS1 in liver cells. The approval and successful implementation of this project will reveal the roles and molecular mechanisms of zebrafish BLOS1 in the regulation of hepatocyte fate and the establishment of liver functions, which could provide a theoretical basis for diagnosis and treatment of BLOC1- and BORC-related liver diseases.