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The cysteine metabolic regulation through CSE-transsulfuration pathway is essential in iron-induced oxidative damage

Yong Zhang1, Yijun Xin1, Jie Zhou1

  • 1Metabolism and Disease Research Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.

Redox Report : Communications in Free Radical Research
|June 5, 2026
PubMed

Insights

The cystathionine gamma-lyase (CSE) pathway is vital for protecting the heart from iron overload damage. Enhancing CSE function may offer a new treatment for iron overload cardiomyopathy by reducing oxidative stress.

Area of Science:

  • Cardiovascular Biology
  • Metabolic Pathways
  • Oxidative Stress Research

Background:

  • Iron overload cardiomyopathy (IOC) is a significant cause of mortality in iron overload disorders.
  • Oxidative stress plays a critical role in the pathogenesis of IOC.

Purpose of the Study:

  • To investigate the role of cystathionine gamma-lyase (CSE) in iron-induced oxidative cardiac injury.
  • To elucidate the mechanisms by which CSE influences cardiac remodeling and antioxidant defense in iron overload.

Main Methods:

  • Utilized in vivo mouse models of chronic iron overload and in vitro ferric citrate-treated cardiomyocytes.
  • Assessed cardiac function, hypertrophy, fibrosis, and molecular markers of oxidative stress and antioxidant pathways.

Main Results:

  • Genetic deletion of CSE exacerbated iron overload-induced cardiac dysfunction and fibrosis, linked to reduced SLC7A11 expression and impaired glutathione synthesis.
  • CSE deficiency suppressed the Nrf2/HO-1/GPX4 antioxidant pathway, increasing reactive oxygen species (ROS) production.
  • CSE overexpression in cardiomyocytes attenuated iron-mediated oxidative damage by restoring SLC7A11 and activating the Nrf2/HO-1/GPX4 pathway.

Conclusions:

  • The CSE-transsulfuration pathway is a critical regulator of cysteine metabolism and antioxidant signaling in cardiomyocytes.
  • CSE plays a protective role against iron-induced cardiomyopathy by maintaining redox balance.
  • Targeting the CSE pathway presents a potential therapeutic strategy for treating iron overload cardiomyopathy.
Abstract

Keywords:
Cardiac injuryGPX4Iron overloadNrf2SLC7A11cystathionine γ-lyasecysteineoxidative stress

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