Parkin介导的线粒体自噬及细胞器互作机制

线粒体是细胞生理代谢活动发生的重要场所. 线粒体生发降解平衡是维持能量代谢稳定的重要保障. Parkin作为E3泛素连接酶,通过PINK1/Parkin、LC3等多种信号参与调控线粒体自噬过程. 此外,Parkin还能够影响线粒体相关内质网膜、调控细胞器间钙流,在线粒体-内质网对话过程中调控溶酶体途径介导的线粒体自噬. 脂肪组织是研究线粒体调节机制的理想模型：寒冷刺激诱导富含线粒体的米色脂肪生成;移除刺激后,组织中线粒体消失恢复为白色脂肪,但线粒体稳定性的调控机理目前仍有很多未知. 本文综述Parkin介导线粒体自噬途径的最新研究进展,及其参与线粒体、内质网、溶酶体等不同细胞器间相互作用的调控机制.

Parkin-mediated Mitophagy and Organelle Contacts

Mitochondria is an major organelle for cellular physiology and metabolism. The homeostasis of mitochondrial biogenesis and degradation is important in maintaining the stability of energy metabolism. Mitophagy is regulated by PINK1/Parkin and LC3 signaling. Parkin, as an E3 ubiquitin ligase, mediates the process of mitochondrial degradation. Parkin is also involved in many other intracellular metabolic activities, such as regulating mitochondrial associated membrane (MAM) and controlling calcium flow in-between organelles. In response to external stimuli like chronic cold exposure, with abundant mitochondria biogenesis, beige adipocytes are generated in the white adipose tissue. Following the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype. Beige adipocyte is an ideal model to study the mechanism of mitochondrial regulation. However, the regulatory mechanism of mitochondrial homeostasis is still unclear. We have reviewed recent studies of novel mechanism on Parkin-mediated mitophagy, and furthermore, the regulatory mechanisms of organelle contacts between mitochondria, endoplasmic reticulum and lysosome.