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Ferroptosis in organ ischemia–reperfusion injuries: recent advancements and strategies

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Abstract

Ferroptosis is a newly discovered type of regulated cell death participated in multiple diseases. Different from other classical cell death programs such as necrosis and apoptosis, ferroptosis involving iron-catalyzed lipid peroxidation is characterized by Fe2+ accumulation and mitochondria alterations. The phenomenon of oxidative stress following organ ischemia–reperfusion (I/R) has recently garnered attention for its connection to the onset of ferroptosis and subsequent reperfusion injuries. This article provides a comprehensive overview underlying the mechanisms of ferroptosis, with a further focus on the latest research progress regarding interference with ferroptotic pathways in organ I/R injuries, such as intestine, lung, heart, kidney, liver, and brain. Understanding the links between ferroptosis and I/R injury may inform potential therapeutic strategies and targeted agents.

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Abbreviations

I/R:

Ischemia–reperfusion

IRI:

Ischemia–reperfusion injury

OIRIs:

Organ ischemia–reperfusion injuries

RCD:

Regulated cell death

ROS:

Reactive oxygen species

PUFA:

Polyunsaturated fatty acid

LOX:

Lipoxygenase

Lipid-OOH:

Lipid peroxides

TF:

Transferrin

TfR1:

Transferrin receptor protein-1

STEAP3:

Prostate six-transmembrane epithelial antigen 3

DMT1:

Divalent metal transporter 1

LIP:

Labile iron pool

PCBP1:

Poly-(rC)-binding protein 1

PCBP2:

Poly-(rC)-binding protein 2

FPN1:

Ferroportin

SLC7A11:

Solute carrier family 7 member 11

xCT:

Cysteine/glutamate transporter

SLC3A2:

Solute carrier family 3 member 2

4F2hc:

4F2 heavy chain

GSH:

Glutathione

•OH:

Hydroxyl radicals

O2• − :

Superoxide anions

H2O2:

Hydrogen peroxide

GPX:

Glutathione peroxidases

Lipid-OH:

Lipid alcohol

GSSG:

Glutathione disulfide

GR:

Glutathione reductase

NADPH:

Nicotinamide-adenine dinucleotide phosphate

FA:

Fatty acid

PL:

Phospholipid

SFA:

Saturated fatty acid

MUFA:

Monounsaturated fatty acid

PUFA:

Polyunsaturated fatty acid

ACSL4:

Acyl-CoA synthetase long-chain family member-4

LPCAT3:

Lysophosphatidylcholine acyltransferase-3

PE:

Phosphatidylethanolamine

AA:

Arachidonic acid

AdA:

Adrenic acid

MDA:

Malondialdehyde

4-HNE:

4-Hydroxy-2-nonenal

IIRI:

Intestinal ischemia–reperfusion injury

CAT:

Capsiate

TRPV1:

Transient receptor potential cation channel subfamily V member 1

H/R:

Hypoxia-reoxygenation

Sp1:

Special protein 1

APG:

Apigenin-7-O-β-D-(-6″-p-coumaroyl)-glucopyranoside

HO-1:

Heme oxygenase 1

MAO-B:

Monoamine oxidase b

ALI:

Acute lung injury

Nrf2:

Nuclear factor erythroid 2-related factor 2

ARE:

Antioxidant reaction element

Nrf2−/− :

Nuclear factor erythroid 2-related factor 2 gene knockout

TERT:

Telomerase reverse transcriptase

STAT3:

Signal transducer and activator of transcription 3

BCAA:

Branched-chain amino acids

L-BAIBA:

L-β-aminoisobutyric acid

LIRI:

Lung ischemia–reperfusion injury

MIRI:

Myocardial ischemia–reperfusion injury

USP7:

Ubiquitin-specific protease 7

FTH1:

Ferritin heavy chain 1

ALOX15:

Arachidonate 15-lipoxygenase

15-HpETE:

15-Hydroperoxyeicosatetraenoic acid

Pgc1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

RNF34:

Ubiquitin ligase ring finger protein 34

KMT2B:

Lysine-specific methyltransferase 2B

RFK:

Riboflavin kinase

TNF:

Tumor necrosis factor

NOX2:

Nicotinamide-adenine dinucleotide phosphate oxidase 2

ATF3:

Activating transcription factor 3

FANCD2:

Fanconi anemia complementation group D2

RIRI:

Renal ischemia–reperfusion injury

AKI:

Acute kidney injury

Dex:

Dexmedetomidine

α2-AR:

α2-Adrenergic receptor

OGD/R:

Oxygen–glucose deprivation and reoxygenation

USC:

Urine-derived stem cell

USC-Exo:

Urine-derived stem cell-derived exosome

TUG1:

Taurine-upregulated gene 1

SRSF1:

Serine/arginine splicing factor 1

IRE1:

Inositol requiring enzyme 1

JNK:

C-Jun NH2-terminal kinases

CCL2:

Chemokine (C–C motif) ligand 2

CCL7:

Chemokine (C–C motif) ligand 7

HIRI:

Hepatic ischemia–reperfusion injury

LT:

Liver transplantation

Ptgs2:

Prostaglandin-endoperoxide synthase 2

TMEM16A:

Transmembrane member 16A

MSC-Exo:

Mesenchymal stem cell-derived exosome

miR:

MicroRNA

BMMSC:

Bone marrow mesenchymal stem cell

IREB2:

Iron response element-binding protein 2

MCTR1:

Maresin conjugate 1 in tissue regeneration

DMF:

Dimethyl fumarate

ME1:

Malic enzyme 1

PTEN:

Phosphatase and tensin homolog

mTOR:

Mechanistic target of rapamycin

SREBP1:

Sterol regulatory element-binding protein 1

IS:

Ischemic stroke

CIRI:

Cerebral ischemia–reperfusion injury

NQO1:

Quinone oxidoreductase 1

MCAO/R:

Middle cerebral artery occlusion and reperfusion

ELA:

Elabela

APJ:

Apelin receptor

NLRP3:

Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3

FACL4:

Fatty acid-CoA ligase 4

PGE2:

Prostaglandin E2

COX:

Cyclooxygenase

NCOA4:

Nuclear receptor coactivator 4

SOD:

Superoxide dismutase

LDH:

Lactate dehydrogenase

LPO:

Lipid peroxidase

HETE:

Hydroxyeicosatetraenoic acid

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

HNF4:

Hepatocyte nuclear factor-4

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  1. Xiaoyu Luan and Peng Chen have contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China

    Xiaoyu Luan, Peng Chen, Longyu Miao, Xinying Yuan, Chaoqun Yu & Guohu Di

  2. Institute of Stem Cell and Regenerative Medicine, School of Basic Medicine, Qingdao University, Qingdao, China

    Peng Chen & Guohu Di

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  1. Xiaoyu Luan
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  3. Longyu Miao
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Contributions

LXY: Conceptualization, Modification, Visualization, Writing—original draft, Writing—review and editing. CP: Conceptualization, Supervision. MLY: Software, Visualization. YXY: Literature checking. YCQ: Literature checking. DGH: Conceptualization, Supervision, Writing—review and editing. All authors have read and approved the final manuscript.

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Correspondence to Guohu Di.

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Luan, X., Chen, P., Miao, L. et al. Ferroptosis in organ ischemia–reperfusion injuries: recent advancements and strategies. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04978-2

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