The Ben May Department for Cancer Research, The University of Chicago, USA.
The Ben May Department for Cancer Research, The University of Chicago, USA; The Committee on Cancer Biology, The University of Chicago, USA.
Semin Cancer Biol. 2017 Dec;47:110-124. doi: 10.1016/j.semcancer.2017.04.008. Epub 2017 Apr 24.
Mitophagy is a selective mode of autophagy in which mitochondria are specifically targeted for degradation at the autophagolysosome. Mitophagy is activated by stresses such as hypoxia, nutrient deprivation, DNA damage, inflammation and mitochondrial membrane depolarization and plays a role in maintaining mitochondrial integrity and function. Defects in mitophagy lead to mitochondrial dysfunction that can affect metabolic reprogramming in response to stress, alter cell fate determination and differentiation, which in turn affects disease incidence and etiology, including cancer. Here, we discuss how different mitophagy adaptors and modulators, including Parkin, BNIP3, BNIP3L, p62/SQSTM1 and OPTN, are regulated in response to physiological stresses and deregulated in cancers. Additionally, we explore how these different mitophagy control pathways coordinate with each other. Finally, we review new developments in understanding how mitophagy affects stemness, cell fate determination, inflammation and DNA damage responses that are relevant to understanding the role of mitophagy in cancer.
自噬是一种选择性的自噬模式，其中线粒体被特异地靶向到自噬溶酶体中进行降解。自噬是由缺氧、营养剥夺、DNA 损伤、炎症和线粒体膜去极化等应激激活的，在维持线粒体完整性和功能方面发挥作用。自噬的缺陷导致线粒体功能障碍，这可能会影响对压力的代谢重编程，改变细胞命运的决定和分化，进而影响疾病的发病率和病因，包括癌症。在这里，我们讨论了不同的自噬衔接蛋白和调节剂，包括 Parkin、BNIP3、BNIP3L、p62/SQSTM1 和 OPTN，如何响应生理应激而被调节，以及在癌症中如何失调。此外，我们还探讨了这些不同的自噬调控途径如何相互协调。最后，我们综述了理解自噬如何影响干性、细胞命运决定、炎症和 DNA 损伤反应的新进展，这些进展与理解自噬在癌症中的作用有关。
