HIF-1α regulates mitochondria function for oxidative stress and autophagy during oocyte maturation
2025
Wen-Lin Pan | Rui-Jie Ma | Yu-Xuan Hou | Yue Wang | Shao-Chen Sun
Hypoxia-inducible factor-1α (HIF-1α) serves as a crucial transcription factor that is pivotal in regulating the cellular response to low-oxygen conditions, and it is also involved in multiple cellular processes under normoxic conditions. During follicular development, oocyte maturation requires massive energy which leads to oxygen decrease and forms physiological hypoxia. HIF-1α is activated to ensure the adaption of follicles to the hypoxic environment and maintain normal development. In the current research, we explored the impacts of HIF-1α activity on oocyte maturation. The findings indicated that the suppression of HIF-1α led to defects in oocyte polar body extrusion. Additionally, mitochondrial dysfunction was detected, manifested by a reduction in mitochondrial membrane potential, the number of mitochondria, and ATP production. Further analysis showed that HIF-1α affected Fis1 and DRP1 for mitochondria dynamics, which further induced Parkin-related mitophagy. This led to a further elevation in ROS levels, thereby causing oxidative stress and triggering early apoptosis. Moreover, the autophagy level in oocytes increased, and at the same time, there are abnormalities in lysosomes. Overall, our findings indicated that HIF-1α maintains oocyte homeostasis and developmental potential by regulating redox balance, mitochondrial function, apoptosis, and autophagy-lysosomal pathways for meiotic maturation.
显示更多 [+] 显示较少 [-]