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Important molecular mechanisms in ferroptosis

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Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Ferroptosis is a type of cell death that is caused by the oxidation of lipids and is dependent on the presence of iron. It was first characterized by Brent R. Stockwell in 2012, and since then, research in the field of ferroptosis has rapidly expanded. The process of ferroptosis-induced cell death is genetically, biochemically, and morphologically distinct from other forms of cellular death, such as apoptosis, necroptosis, and non-programmed cell death. Extensive research has been devoted to comprehending the intricate process of ferroptosis and the various factors that contribute to it. While the majority of these studies have focused on examining the effects of lipid metabolism and mitochondria on ferroptosis, recent findings have highlighted the significant involvement of signaling pathways and associated proteins, including Nrf2, P53, and YAP/TAZ, in this process. This review provides a concise summary of the crucial signaling pathways associated with ferroptosis based on relevant studies. It also elaborates on the drugs that have been employed in recent years to treat ferroptosis-related diseases by targeting the relevant signaling pathways. The established and potential therapeutic targets for ferroptosis-related diseases, such as cancer and ischemic heart disease, are systematically addressed.

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Abbreviations

ACSL4:

Acyl-CoA synthetase long chain family member 4

ALOX12:

Arachidonic 12-lipoxygenase

ALOX15:

Arachidonic 15-lipoxygenase

ATF3:

Activation transcription factor 3

Bach1:

BTB and CNC homology 1

BRD4:

Bromodomain-containing protein 4

CDK1:

Cyclin-dependent kinase 1

CYP1B1:

Cytochrome P450 1B1

Cys:

Cystine

DMF:

Dimethyl fumarate

DPP4:

Dipeptidyl peptidase 4

EMP1:

Epithelial membrane protein 1

FECH:

Ferrochelatase

FPN:

Ferroportin

FPN1:

Ferroportin 1

FTH:

Ferritin heavy chain

FTH1:

Ferritin heavy chain 1

FTL:

Ferritin light chain

G6PD:

Glucose-6-phosphate dehydrogenase

GCLC:

Glutamate-cysteine ligase catalytic subunit

GCLM:

Glutamate-cysteine ligase modifier subunit

GPX4:

Glutathione peroxidase 4

GSH:

Glutathione

H2Bub1:

H2B ubiquitination modification

HCC:

Hepatocellular carcinoma

HO-1:

Heme oxygenase-1

HSF1:

Heat shock factor 1

HSPB1:

Heat shock protein family B member 1

HSPE1:

Heat shock protein family E member 1

IMA:

Imatinib

JAK:

Janus kinase

LSH:

Lymphoid-specific helicase

MCL1:

Myeloid cell leukemia-1

NADPH:

Nicotinamide adenine dinucleotide phosphate

NCOA4:

Nuclear receptor co-activator protein 4

NEDD4L:

Neural precursor cell expressed developmentally downregulated 4-like

NQO1:

NAD(P)H quinone oxidoreductase 1

Nrf2:

Nuclear factor-erythroid 2-related factor 2

OGD/R:

Oxygen-glucose deprivation and reoxygenation

PLB:

Plumbagin

ROS:

Reactive oxygen species

SAT1:

Spermidine/spermine N1-acetyltransferase 1

SIRT6:

Sirtuin 6

SKP2:

S-phase kinase-associated protein 2

SLC40A1:

Solute carrier family 40 member 1

SLC7A11:

Solute carrier family 7 member 11

STAT3:

Signal transducer and activator of transcription 3

TAZ:

Transcriptional coactivator with PDZ-binding motif

TEAD:

TEA/ATTS domain

TFAP2A:

Transcription factor AP2 alpha

TFRC:

Transferrin receptor

TGF-β:

Transforming growth factor beta

THSWD:

Tao Hong Si Wu Tang

TNFAIP1:

TNF alpha-induced protein 1

Tyk2:

Tyrosine kinase 2

Ub:

Ubiquitin

Usp7:

Ubiquitin-specific protease 7

YAP:

Yes-Association protein

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A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).

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  1. Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China

    Lunmeng Lai, Menglei Tan, Mingming Hu, Xiyue Yue, Lulu Tao, Yanru Zhai & Yunsen Li

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  1. Lunmeng Lai
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  2. Menglei Tan
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Lai and Hu were responsible for the main manuscript preparation, while Yue carried out the main proofreading and literature collection. Images 1-6 were produced by Tan,Tao and Zhai. Li carried out direction and topic related guidance. Tan and Lai make subsequent revisions to the article.

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Lai, L., Tan, M., Hu, M. et al. Important molecular mechanisms in ferroptosis. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-05009-w

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