Focused screening of mitochondrial metabolism reveals a crucial role for a tumor suppressor Hbp1 in ovarian reserve

Z. Dong, M. Huang, Z. Liu, P. Xie, Y. Dong, X. Wu, Z. Qu, B. Shen, X. Huang, T. Zhang, J. Li, J. Liu, T. Yanase, Chengji Zhou, Y. Xu

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Granulosa cells (GCs) are tightly associated with fertility and the fate of ovarian follicles. Mitochondria are the central executers of apoptosis. However, the genetic basis underlying mitochondrial modulation in GCs during the ovarian development is poorly understood. Here, CRISPR/Cas9-mediated genetic screening was used to identify genes conferring mitochondrial metabolism in human GCs. The results uncovered roles for several tumor suppressors, including HBP1, in the augmentation of mitochondrial function. Focused analysis revealed that high-mobility group (HMG)-box transcription factor 1 (Hbp1) levels regulate mitochondrial biogenesis, which is associated with global changes in transcription including Tfam. The systemic or granulosa-specific but not oocyte-specific ablation of Hbp1 promoted follicle growth and oocyte production, and is associated with the reduced apoptotic signals in mouse GCs. Consistent with increased mitochondrial function and attenuated GC apoptosis, the regulation of Hbp1 conferred substantial protection of ovarian reserve. Thus, the results of the present study provide a critical target to understand the control of the reproductive lifespan.

Original languageEnglish (US)
Pages (from-to)1602-1614
Number of pages13
JournalCell Death and Differentiation
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Dong, Z., Huang, M., Liu, Z., Xie, P., Dong, Y., Wu, X., Qu, Z., Shen, B., Huang, X., Zhang, T., Li, J., Liu, J., Yanase, T., Zhou, C., & Xu, Y. (2016). Focused screening of mitochondrial metabolism reveals a crucial role for a tumor suppressor Hbp1 in ovarian reserve. Cell Death and Differentiation, 23(10), 1602-1614. https://doi.org/10.1038/cdd.2016.47