FSP1: a key regulator of ferroptosis

• Published in: Trends in molecular medicine Vol. 29; no. 9; pp. 753 - 764
• Main Authors: Li, Wentao, Liang, Lin, Liu, Siyi, Yi, Hong, Zhou, Yanhong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2023
• Subjects: epigenetic modification; ferroptosis; FSP1; noncoding RNA; regulation mechanism; epigenetic modification; ferroptosis; noncoding RNA; regulation mechanism; FSP1
• ISSN: 1471-4914; 1471-499X; 1471-499X
• DOI: 10.1016/j.molmed.2023.05.013

Ferroptosis suppressor protein 1 (FSP1) is a glutathione-independent ferroptosis inhibitor molecule, which exerts a ferroptosis inhibition role parallel to glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4).The myristoylation of the N-terminal of FSP1 is the key reason for its membrane localization and ferroptosis inhibition.FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis, and nonclassical redox cycle of vitamin K with FSP1 participation are important ways for FSP1 to regulate ferroptosis.FSP1 is regulated by upstream factors such as transcription factors and noncoding RNA and is subject to epigenetic modifications such as acetylation and methylation, thus affecting the progress of ferroptosis-related diseases. Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules of ferroptosis. FSP1 functions through the FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and the vitamin K redox cycle. FSP1 is regulated by upstream factors, including transcription factors and noncoding RNA (ncRNA), and is subject to epigenetic modifications, which affect the progress of FSP1-related diseases. FSP1 is closely associated with the poor prognosis of malignant tumors and plays an important role in disease treatment. This review aims to provide a comprehensive understanding of the role of FSP1 in ferroptosis regulation by summarizing regulatory pathways, possible mechanisms involving FSP1, and the relationship between FSP1 and disease prognosis and treatment. Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules of ferroptosis. FSP1 functions through the FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and the vitamin K redox cycle. FSP1 is regulated by upstream factors, including transcription factors and noncoding RNA (ncRNA), and is subject to epigenetic modifications, which affect the progress of FSP1-related diseases. FSP1 is closely associated with the poor prognosis of malignant tumors and plays an important role in disease treatment. This review aims to provide a comprehensive understanding of the role of FSP1 in ferroptosis regulation by summarizing regulatory pathways, possible mechanisms involving FSP1, and the relationship between FSP1 and disease prognosis and treatment.