线粒体生发降解平衡是维持能量代谢稳定的重要保障。脂肪组织是研究线粒体稳定性调节机制的理想模型：寒冷刺激能激活肾上腺素受体β3-AR信号，诱导生成富含线粒体的米色脂肪；移除刺激后，线粒体被快速清除并恢复为白色脂肪组织，然而目前线粒体稳定性的调控机理还有很多未知。线粒体自噬一般受到PINK1/Parkin、LC3等多种信号调控。我们研究mt-Keima小鼠米色脂肪生发降解模型和PINK1/Parkin荧光示踪脂肪细胞模型，发现β3-AR信号对脂肪线粒体自噬水平有抑制作用。在此基础上提出本项目研究：1）米色脂肪中PINK1/Parkin在线粒体自噬清除过程中的功能；2）β3-AR信号激活PKA途径，通过磷酸化作用介导线粒体内膜蛋白MIC60- PINK1/Parkin之间的互作，从而抑制线粒体自噬的机制。本项目研究将对揭示脂肪组织线粒体稳定性调控机制，为代谢性疾病的预防和治疗提供新的策略和途径。

The homeostasis of mitochondrial biogenesis and degradation is important in maintaining the stability of energy metabolism. Mitochondria mis-regulation exists in several human diseases, such as obesity, diabetes and cancer. Adipose tissue is an ideal model to study the mechanism of mitochondrial regulation. Beige adipocytes are an inducible form of mitochondria-enriched thermogenic adipocytes, which emerge in response to external stimuli like chronic cold exposure with the activation of β3-AR. Following the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype. As we knew, mitophagy is mainly regulated by the signaling pathway of PINK1/Parkin, LC3 et al. However, the regulatory mechanism of this transition is still not clear..We have developed an mitochondrial biogenesis and degradation model in mt-Keima mouse and PINK1-GFP/YFP-Parkin over-expression model in mouse immortalized adipocytes. And found that β3-AR is able to attenuate the mitophagy flux in adipose tissue. Based on the phenomenon, our study will systematically analyze the function of PINK1/Parkin in regulating the process of mitochondrial clearance in beige adipose tissue. Explore the roles of β3-AR signal stimulated PKA pathway in controlling PINK1/Parkin-mediated mitophagy through mitochondrial inner membrane MIC60/Mitofilin in beige adipose tissue. This study will distinguish the regulatory mechanisms of PINK1/Parkin-mediated mitophagy in beige adipose, which will bring a fresh perspective on the prevention and treatment of diseases caused by metabolic disorders.