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Updated: Aug 13, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

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NEDD4L facilitates granulosa cell ferroptosis by promoting GPX4 ubiquitination and degradation

Hong Tang1, Xiaomei Jiang1, Yu Hua1

  • 11Departments of Gynaecology and Obstetrics Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Endocrine Connections
|January 20, 2023
PubMed
Abstract

Insights

NEDD4L promotes granulosa cell (GC) ferroptosis by degrading GPX4, contributing to polycystic ovary syndrome (PCOS) development. This study clarifies a key mechanism in PCOS pathogenesis.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Molecular Medicine

Background:

  • Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age, characterized by androgen excess and ovarian dysfunction.
  • Granulosa cell (GC) death is implicated in PCOS development, but the underlying mechanisms remain poorly understood.

Purpose of the Study:

  • To investigate the role of NEDD4L in GC death and its potential contribution to PCOS pathogenesis.
  • To elucidate the molecular mechanism by which NEDD4L influences GC viability and ferroptosis.

Main Methods:

  • NEDD4L expression analysis in PCOS databases and mouse models.
  • Cell viability assays (CCK-8, FDA staining) in KGN cells.
  • Assessment of ferroptosis markers (ELISA, immunofluorescence).
  • Co-immunoprecipitation to verify protein interactions.

Main Results:

  • NEDD4L expression is elevated in PCOS models.
  • NEDD4L inhibits KGN cell viability and induces ferroptosis by increasing iron and ROS, and decreasing glutathione.
  • NEDD4L directly interacts with GPX4, promoting its ubiquitination and degradation.

Conclusions:

  • NEDD4L facilitates GC ferroptosis through GPX4 degradation, highlighting a novel mechanism in PCOS.
  • Targeting NEDD4L-mediated ferroptosis may offer a therapeutic strategy for PCOS.
Keywords:
GPX4NEDD4LPCOSferroptosisubiquitination

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