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Potential role of SIRT1 in cell ferroptosis

Yueming Zhang, Fanxiao Kong, Nan Li, Lina Tao, Jinghui Zhai, Jie Ma, Sixi Zhang

2025Frontiers in Cell and Developmental Biology12 citationsDOIOpen Access PDF

Abstract

Ferroptosis is a novel form of cell death that uniquely requires iron and is characterized by iron accumulation, the generation of free radicals leading to oxidative stress, and the formation of lipid peroxides, which distinguish it from other forms of cell death. The regulation of ferroptosis is extremely complex and is closely associated with a spectrum of diseases. Sirtuin 1 (SIRT1), a NAD + -dependent histone deacetylase, has emerged as a pivotal epigenetic regulator with the potential to regulate ferroptosis through a wide array of genes intricately associated with lipid metabolism, iron homeostasis, glutathione biosynthesis, and redox homeostasis. This review provides a comprehensive overview of the specific mechanisms by which SIRT1 regulates ferroptosis and explores its potential therapeutic value in the context of multiple disease pathologies, highlighting the significance of SIRT1-mediated ferroptosis in treatment strategies.

Topics & Concepts

Histone deacetylaseSirtuinCell biologyRegulatorEpigeneticsProgrammed cell deathOxidative stressGPX4BiologyContext (archaeology)HistoneCell fate determinationHomeostasisNAD+ kinaseTranscription factorApoptosisBiochemistryGeneSuperoxide dismutaseEnzymeGlutathione peroxidasePaleontologyFerroptosis and cancer prognosisCancer-related molecular mechanisms researchRNA modifications and cancer
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