Elevated PINK1 in mouse oocytes disrupted meiosis and mitochondrial quality control, while active RAB8A partly rescued aged-oocyte quality.
Evidence
Preclinical mouse oocyte experiments measured PINK1 levels in aged oocytes and tested Pink1 overexpression, mitochondrial phenotypes, embryo development, and GTP-bound RAB8A rescue.
Caveat
The findings come from murine oocyte and overexpression experiments, so they do not establish the same mechanism or fertility effect in humans.
Simplified
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 (ROS) level, severely disrupted spindle/chromosome organization, and abnormal . 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.
Key numbers
32%
Decrease in Levels
content in overexpressing vs. control .
30.1%
First Polar Body Extrusion Rate
Rate of in overexpressing vs. control .
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