Loss of PINK1 impairs mitophagy and accelerates ovarian aging independent of Parkin.

Xinxin Zeng, Huihui Xie, Wandi Zhang, Yongxing Yu, Mengchen Wang, Yuqing Jiang, Ruizhi Guo, Yingpu Sun, Qingling Yang

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Provincial Obstetrical and Gynecological Disease (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. · pubmed

Paper

Abstract

PINK1 and Parkin are central regulators of mitophagy, a quality-control process essential for mitochondrial homeostasis and implicated in aging. However, their specific roles in ovarian physiology remain unclear. Here, we show that Pink1 deletion in mice leads to decreased ovarian weight, diminished ovarian reserve, and reduced oocyte quality, accompanied by increased granulosa cell apoptosis, accelerated ovarian ageing, and impaired fertility. Pink1 deficiency also compromises ovulation efficiency, increases oocyte cytoplasmic fragmentation, and disrupts meiotic spindle assembly, resulting in markedly reduced developmental competence of early embryos. Mechanistically, bulk and single-cell RNA sequencing reveal that loss of PINK1 impairs mitophagy and promotes transcriptional signatures of ovarian aging. In contrast, Parkin deletion exerts minimal effects on mitophagy, mitochondrial function, or ovarian physiology. Together, these findings identify PINK1, but not Parkin, as a critical regulator of ovarian aging through modulation of mitophagy.

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Research summary

Loss of PINK1 impairs mitophagy and accelerates ovarian aging independent of Parkin. The study identifies PINK1 as a critical regulator of ovarian aging, linking mitochondrial quality control to the aging process, which is central to understanding and potentially mitigating age-related decline in reproductive health.

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