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Peroxisome Biogenesis Factor 10 Upregulation Promotes Cardiomyocyte Ferroptosis and Glutathione Peroxidase 4

Jing Li1, Xiaofeng Ma1

  • 1The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang City.

Kardiologiia
|April 2, 2026
PubMed

Insights

Peroxisome factor PEX10 promotes ferroptosis in heart injury by suppressing GPX4. Targeting the PEX10-GPX4 pathway may offer new treatments for myocardial ischemia-reperfusion injury.

Area of Science:

  • Cardiovascular Biology
  • Cell Death Mechanisms
  • Oxidative Stress Research

Background:

  • Myocardial ischemia-reperfusion (I/R) injury causes significant cardiomyocyte death via oxidative stress.
  • Ferroptosis, an iron-dependent cell death, is implicated, but its regulators are unknown.
  • Understanding ferroptosis modulators is crucial for treating I/R injury.

Purpose of the Study:

  • To investigate the role of peroxisome biogenesis factor 10 (PEX10) in ferroptosis during myocardial I/R injury.
  • To elucidate the molecular mechanism by which PEX10 influences ferroptosis.
  • To assess the therapeutic potential of targeting the PEX10-GPX4 axis.

Main Methods:

  • Analyzed PEX10 expression in I/R datasets and cell models (oxygen-glucose deprivation/reoxygenation).
  • Utilized siRNA to silence PEX10, assessing cell viability, oxidative stress, iron levels, and ferroptosis markers.
  • Examined GPX4 transcriptional regulation and conducted rescue experiments with RSL3 and Ferrostatin-1.

Main Results:

  • PEX10 was upregulated in I/R injury and OGD/R-treated cells.
  • PEX10 knockdown enhanced cell viability and reduced oxidative stress, iron accumulation, and ferroptosis.
  • PEX10 suppressed GPX4 transcription; Ferrostatin-1 mimicked PEX10 knockdown's protective effects.

Conclusions:

  • PEX10 is a novel mediator of ferroptosis in myocardial I/R injury.
  • PEX10 exerts its effect by repressing GPX4 transcription.
  • Targeting the PEX10-GPX4 axis presents a potential therapeutic strategy for I/R injury.

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