Ferroptosis and Its Role in Chronic Diseases

Hu, Weijun; Liu, Kehong; Zhu, Hong; Zhao, Chong; Hu, Hongbo; Yin, Shutao

doi:10.3390/cells11132040

Cited by 58 publications

(41 citation statements)

References 228 publications

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“…Since ferroptosis has been associated with several diseases [9][10][11][12][13]42,43 , our findings might have implications of medical interest. Concretely, ferroptosis propagation has been proposed to play a role in the formation of necrotic tissue in intestinal epithelium 44 , heart tissue [45][46][47] , excitotoxicity in brain 48 and renal tubula 23 , which underpins the patho-physiological relevance of this cell-contact dependent process 7,23,25 .…”

Section: Discussionmentioning

confidence: 87%

“…While lipid peroxides accumulation has been identified as key event during ferroptosis, the molecular mechanisms governing ferroptosis regulation and execution remain poorly understood 7,8 . Ferroptosis has been associated with a number of diseases, including neurodegeneration, kidney failure or stroke [9][10][11][12][13] . In addition, induction of ferroptosis holds potential as an anti-cancer treatment strategy for refractory cancers.…”

Section: Introductionmentioning

confidence: 99%

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Ferroptosis propagates to neighboring cells via cell-cell contacts

Roeck

Vorndran

García‐Sáez

2023

Preprint

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Ferroptosis is an iron-dependent form of regulated cell death characterized by accumulation of peroxidized lipids and plasma membrane disruption, whose molecular mechanism of execution remains poorly understood. Here, we developed a new optogenetic system, Opto-GPX4Deg, for light-induced degradation of the lipid reducing protein GPX4, which allows controlled ferroptosis induction with high precision in time and space. By using Opto-GPX4Deg to study cell death dynamics within the cellular population, we found that lipid peroxidation, followed by ferroptotic death, spread to neighboring cells in a distance-dependent manner. Remarkably, ferroptosis propagation showed a strong dependency on cell confluence and preferentially affected adjacent cells. Our findings establish cell death propagation as a feature of ferroptosis and provide new understanding of the mechanism involved.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Ferroptosis propagates to neighboring cells via cell-cell contacts

Roeck

Vorndran

García‐Sáez

2023

Preprint

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“…As a newly discovered form of regulated cell death, ferroptosis is morphologically, chemically, and genetically different from apoptosis, autophagy, necroptosis, and pyroptosis, and is regulated by its unique metabolism and regulatory mechanism [ 1 , 3 ]. With the increasing studies in recent years, more and more evidence demonstrated that ferroptosis may play a significant role in multiple physiological and pathological processes, such as embryonic development, cancer, neurodegeneration disease, and organ disorders caused by drug-induced toxicity or ischemia/reperfusion injury (IRI) [ 4 , 5 , 6 , 7 , 8 , 9 ]. In cancer, ferroptosis is reported to play an essential role in suppressing spontaneous tumorigenesis in mouse models [ 10 , 11 ]; many cancer cells resistant to conventional therapies were found to be susceptible to ferroptosis [ 12 , 13 ], suggesting that the induction of ferroptosis in cancer cells is a promising anti-tumor strategy.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis Regulated by Hypoxia in Cells

Zheng

Liang

Zhang

2023

Cells

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Ferroptosis is an oxidative damage-related, iron-dependent regulated cell death with intracellular lipid peroxide accumulation, which is associated with many physiological and pathological processes. It exhibits unique features that are morphologically, biochemically, and immunologically distinct from other regulated cell death forms. Ferroptosis is regulated by iron metabolism, lipid metabolism, anti-oxidant defense systems, as well as various signal pathways. Hypoxia, which is found in a group of physiological and pathological conditions, can affect multiple cellular functions by activation of the hypoxia-inducible factor (HIF) signaling and other mechanisms. Emerging evidence demonstrated that hypoxia regulates ferroptosis in certain cell types and conditions. In this review, we summarize the basic mechanisms and regulations of ferroptosis and hypoxia, as well as the regulation of ferroptosis by hypoxia in physiological and pathological conditions, which may contribute to the numerous diseases therapies.

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“…Ferroptosis is characterized by iron overload, the accumulation of lethal lipid hydroperoxides, a weakened antioxidant capacity, and mitochondrial changes such as smaller mitochondria, diminished or absent mitochondrial cristae, and ruptured mitochondrial outer membranes [ 7 , 8 ]. These manifestations are distinct from those of apoptosis, necroptosis, and pyroptosis [ 9 ]. In ferroptosis, lipid peroxidation is caused by reactive oxygen species (ROS) derived from the Fenton reaction, and the accumulation of these peroxides on cellular membranes can damage the membranes and cause cell death [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Fatty Acid β-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions

Chen¹,

Wu²,

Lei³

et al. 2023

Endocrinol Metab

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Background: Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD.Methods: We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells.Results: In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe<sup>2+</sup>), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells.Conclusion: Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation.

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Ferroptosis and Its Role in Chronic Diseases

Cited by 58 publications

References 228 publications

Ferroptosis propagates to neighboring cells via cell-cell contacts

Ferroptosis propagates to neighboring cells via cell-cell contacts

Ferroptosis Regulated by Hypoxia in Cells

Inhibition of Fatty Acid β-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions

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