PINK1 functions in mitophagy and mitochondrial homeostasis during mice oocyte maturation

Abstract

Background: As a serine/threonine kinase, PINK1 (PTEN-induced putative kinase 1) is widely expressed in mammalian tissues and cells, especially in the female reproductive system. However, its role in meiotic oocytes remains obscure. Here, we report that murine oocytes overexpressing Pink1 are unable to completely progress through meiosis. Results: In the present study, we found that PINK1 protein levels in aged oocytes showed a substantial increase. Importantly, we revealed that murine oocytes overexpressing Pink1 are unable to completely progress through meiosis. This leads to inadequate mitochondrial redistribution, an elevated reactive oxygen species (ROS) level, severely disrupted spindle/chromosome organization, and abnormal mitophagy. Furthermore, we noted that elevated Pink1 expression significantly compromises the developmental ability of the mouse early embryo. In addition, we revealed that RAB8A activity is a key factor for PINK1-mediated mitophagy in old oocytes and active guanosine triphosphate (GTP)-bound state RAB8A could partially rescue the quality of aged oocytes by promoting the formation of autolysosome. Conclusions: Collectively, our data display critical functions for PINK1 in meiotic progression and mitochondrial homeostasis in murine oocytes, and RAB8A activity is required for PINK1-mediated mitophagy in senescent oocytes.