线粒体参与脂肪酸的β氧化和甘油磷脂、鞘磷脂等磷脂的合成，在脂代谢中发挥关键作用。线粒体稳态是指线粒体分裂和融合，线粒体自噬和线粒体生物发生的平衡。线粒体稳态异常与很多代谢综合征的发生密切相关。但脂肪代谢如何影响线粒体稳态，以及线粒体稳态异常如何导致非酒精性脂肪肝病的发生的机制尚不清楚。我们前期的研究发现，棕榈酸PA促进线粒体自噬的受体蛋白FUNDC1的泛素化降解进而影响线粒体稳态。本申请计划深入分析脂肪代谢影响线粒体稳态和线粒体功能的分子机制，特别是脂代谢影响线粒体自噬及线粒体与内质网互作（MAM）的分子细节，通过用不同水平棕榈酸的高脂饲料喂养FUNDC1敲除小鼠和转基因小鼠，探讨线粒体稳态参与非酒精性脂肪肝病发生、发展中的作用。

Mitophagy play an essential role in fatty acid oxidation, phospholipids synthesis lipid metabolism. Mitochondria are dynamic organelles undergoing constant fusion and fission, mitochondrial biogenesis and degradation to maintain their homeostasis. Dysfunction of mitochondrial homeostasis closely related with many metabolic syndromes. Until now, if fat acid metabolism affects mitochondrial homeostasis, and dysfunction of mitochondrial homeostasis lead to the occurrence of nonalcoholic fatty liver disease mechanism is still unclear. We found that the palmitic acid PA promotes mitophagy receptors FUNDC1 ubiquitin degradation mediated mitochondrial homeostasis in unpunished data. In this study, we will focus on how fat acid metabolism affect mitochondrial homeostasis and mitochondrial function, especially in lipid metabolism how involve in mitophagy, the interaction of mitochondria with endoplasmic reticulum by MAM. We also will take system biology and molecular cell biology approaches to understand the molecular details of PA induced non-alcoholic fatty liver diseases models from FUDNC1 KO or overexpression mice. Our project will reveal the intrinsic links of mitochondrial homeostasis with MAMs in PA induced hepatic diseases.