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Volume 42 Issue 3
Mar.  2026
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Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(3): 726-732

Dual ferroptosis suppressor protein 1-coenzyme Q10 and dihydroorotate dehydrogenase pathways in ferroptosis of hepatocellular carcinoma： Mechanisms and its clinical significance

DOI: 10.12449/JCH260331
  • 1.

    Department of Geriatrics，The First Hospital of Jilin University，Changchun 130021，China

  • 2.

    Department of Hepatopancreatobiliary Medicine，The First Hospital of Jilin University，Changchun 130021，China

Research funding:

Jilin Provincial Special Program for Healthcare Talents (JLSRCZX2025-018)

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  • Corresponding author: WANG Yuehui， yuehuiwang300@jlu.edu.cn （ORCID： 0009-0003-3103-1504）
  • Received Date: 2025-09-23
  • Accepted Date: 2025-10-14
  • Published Date: 2026-03-25
    Abstract
  • Hepatocellular carcinoma （HCC） is a common malignant tumor with a high fatality rate worldwide， with limited overall survival benefits and pronounced drug resistance issues， highlighting the urgent need for novel sensitization strategies and patient stratification systems. Ferroptosis， as an iron-dependent form of lipid peroxidation-driven cell death， is closely associated with tumor treatment responses. In addition to the classic glutathione peroxidase 4 （GPX4）/glutathione （GSH） pathway， the ferroptosis suppressor protein 1 （FSP1）-coenzyme Q10 （CoQ10） pathways and the dihydroorotate dehydrogenase （DHODH） pathway are two newly identified anti-ferroptosis pathways that function at the plasma membrane and mitochondria， respectively， and determine cellular sensitivity to ferroptosis in synergy with GPX4. This article systematically reviews the mechanism of action of the FSP1-CoQ10 and DHODH pathways in HCC and related research advances， proposes related therapeutic strategies， and look forward to its clinical translation and application prospects.

     

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