线粒体自噬在乳腺癌发生发展中的作用及其调控机制  

Research progress in roles and mechanism of mitophagy in breast cancer

作　　者：丁烨 魏佳乐 熊阳[1,2] DING Ye;WEI Jiale;XIONG Yang(School of Pharmaceutical Science,2.Academy of Chinese Medical Science,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]浙江中医药大学中医药科学院,浙江杭州310053

出　　处：《中国药理学与毒理学杂志》2024年第7期533-541,共9页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(82174095);国家级大学生创新创业训练计划(202310344051);浙江省自然科学基金(LZ22H290001);浙江省中医药科技计划(2023ZL362)。

摘　　要：线粒体自噬是细胞通过自噬-溶酶体途径,在自噬相关蛋白的调控下,有选择地清除受损或功能障碍的线粒体以维持线粒体质量和细胞稳态的过程,与多种肿瘤的发生发展密切相关。越来越多研究表明,线粒体自噬在乳腺癌进展中发挥着双重作用。①促进乳腺癌进展:线粒体自噬通过触发能量代谢重编,减少ROS蓄积和维持线粒体稳态来促进乳腺癌细胞的生存和侵袭;②抑制乳腺癌进展:线粒体自噬通过减轻炎症反应和引发线粒体损伤,诱导乳腺癌细胞死亡或凋亡。其相关机制包括①PTEN诱导的激酶1/E3泛素蛋白连接酶(PINK1/Parkin)途径;②线粒体自噬受体相关蛋白途径(包括BNIP3、BNIP3L和FUNDC1);③线粒体分裂途径。本综述总结了线粒体自噬在乳腺癌中的作用、机制以及化疗耐药的研究现状,旨在为乳腺癌的研究和治疗提供参考。Mitophagy is a process by which cells selectively eliminate damaged or dysfunctional mitochondria through the autophagy-lysosomal pathway under the regulation of mitophagy-related proteins to maintain mitochondrial quality and cellular homeostasis,and it is closely related to the occurrence and development of a variety of tumors.Increasing studies have shown that mitophagy plays a dual role in breast cancer progression.①Mitophagy promotes breast cancer cell survival and invasion by triggering energy metabolic reprogramming,reducing ROS accumulation and maintaining mitochondrial homeostasis.②Mitophagy leads to death or apoptosis of breast cancer cells by attenuating inflammatory responses and triggering mitochondrial damage.The relevant mechanisms include①PTEN induced kinase 1,PINK1(PINK1)/Parkin pathway;②mitophagy receptor-associated protein pathway(including BNIP3,BNIP3L and FUNDC1);③mitochondrial division pathway.This review summarizes the role and mechanism of mitophagy in the hopes of providing reference for research and treatment of breast cancer.

关 键 词：乳腺癌 线粒体自噬 PINK1/Parkin 线粒体自噬受体相关蛋白 自噬调节因子 化疗耐药 

分 类 号：R966[医药卫生—药理学] R737.9[医药卫生—药学]