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Review
. 2025 Sep 9:S1471-4914(25)00194-7.
doi: 10.1016/j.molmed.2025.08.006. Online ahead of print.

MAFLD: a ferroptotic disease

Shaojie Cui  1 , Jin Ye  2
Affiliations
Review

MAFLD: a ferroptotic disease

Shaojie Cui et al. Trends Mol Med. .

Abstract

Ferroptosis, a regulated cell death pathway driven by iron-catalyzed lipid peroxidation, has recently been implicated as a major cause of hepatic injury in metabolic dysfunction-associated fatty liver disease (MAFLD). This review highlights how the identification of hyperoxidized peroxiredoxin 3 (PRDX3) as a ferroptosis-specific marker has led to the discovery that ferroptosis contributes to liver injury in MAFLD, and summarizes other emerging evidence connecting ferroptosis to MAFLD pathogenesis. These new findings suggest that dietary fat composition and genetic variants such as PNPLA3(I148M) may affect the progression of MAFLD by regulating cellular sensitivity to ferroptosis. Recognizing MAFLD as a ferroptotic disease provides novel insights into the pathogenesis of the disease, and supports the exploration of ferroptosis as a potential target for therapeutic intervention.

Keywords: VLDL; ferroptosis; hyperoxidized PRDX3; lipid peroxidation; monounsaturated fatty acids; polyunsaturated phospholipids.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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