Ferroptosis and Necroptosis in the Kidney

Belavgeni, Alexia; Meyer, Claudia; Stumpf, Julian; Hugo, Christian; Linkermann, Andreas

doi:10.1016/j.chembiol.2020.03.016

Cited by 156 publications

(118 citation statements)

References 230 publications

(288 reference statements)

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“…Besides a glutathione dependent system, ferroptosis suppressor protein 1 (FSP1) was identified to protect cells from ferroptosis by reducing coenzyme Q10, which acts as a radical scavenger (Bersuker et al , 2019; Doll et al , 2019). Ferroptosis has been associated with several pathologies as reviewed elsewhere (Bebber et al , 2020; Belavgeni et al , 2020; Li et al , 2020).…”

Section: Introductionmentioning

confidence: 99%

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Cell death pathways: intricate connections and disease implications

Kist¹,

Vucic²

2021

The EMBO Journal

169

140

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Various forms of cell death have been identified over the last decades with each relying on a different subset of proteins for the activation and execution of their respective pathway(s). In addition to the three best characterized pathways—apoptosis, necroptosis, and pyroptosis—other forms of regulated cell death including autophagy‐dependent cell death (ADCD), mitochondrial permeability transition pore (MPTP)‐mediated necrosis, parthanatos, NETosis and ferroptosis, and their relevance for organismal homeostasis are becoming better understood. Importantly, it is increasingly clear that none of these pathways operate alone. Instead, a more complex picture is emerging with many pathways sharing components and signaling principles. Finally, a number of cell death regulators are implicated in human diseases and represent attractive therapeutic targets. Therefore, better understanding of physiological and mechanistic aspects of cell death signaling should yield improved reagents for addressing unmet medical needs.

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Section: Introductionmentioning

confidence: 99%

“…Ferroptosis and necroptosis have been implicated in kidney pathologies (Belavgeni et al , 2020), and inhibitors of ferroptosis and necroptosis showed protection in various disease models in mice. However, it is still not completely understood how both different mechanisms work together.…”

Section: Introductionmentioning

confidence: 99%

Cell death pathways: intricate connections and disease implications

Kist¹,

Vucic²

2021

The EMBO Journal

169

140

View full text Add to dashboard Cite

show abstract

“…Indeed, massive reactive oxygen species production has been suggested to induce DNA damage independent of necrosis and apoptosis [ 37 ]. These data, therefore, suggest that that the initial (acute) injury post reperfusion is likely more associated with other (inflammatory) types of cell death (e.g., necrosis, caspase3-independent pyrroptosis, ferroptosis, or necroptosis) rather than apoptosis [ 38 , 39 ]. Indeed, in previous work we have shown that necroptosis inhibitor Nec-1 reduces the positive TUNEL staining 3 h post reperfusion in our model [ 26 ], suggesting that necroptosis is activated shortly following reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury

Decuypere

Hutchinson

Monbaliu

et al. 2020

IJMS

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Renal ischemia-reperfusion (IR) injury leading to cell death is a major cause of acute kidney injury, contributing to morbidity and mortality. Autophagy counteracts cell death by removing damaged macromolecules and organelles, making it an interesting anchor point for treatment strategies. However, autophagy is also suggested to enhance cell death when the ischemic burden is too strong. To investigate whether the role of autophagy depends on the severity of ischemic stress, we analyzed the dynamics of autophagy and apoptosis in an IR rat model with mild (45 min) or severe (60 min) renal ischemia. Following mild IR, renal injury was associated with reduced autophagy, enhanced mammalian target of rapamycin (mTOR) activity, and apoptosis. Severe IR, on the other hand, was associated with a higher autophagic activity, independent of mTOR, and without affecting apoptosis. Autophagy stimulation by trehalose injected 24 and 48 h prior to onset of severe ischemia did not reduce renal injury markers nor function, but reduced apoptosis and restored tubular dilation 7 days post reperfusion. This suggests that trehalose-dependent autophagy stimulation enhances tissue repair following an IR injury. Our data show that autophagy dynamics are strongly dependent on the severity of IR and that trehalose shows the potential to trigger autophagy-dependent repair processes following renal IR injury.

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“…It is characterized by iron accumulation and lipid peroxidation, and morphologically distinct from other forms of regulated cell death [21,195]. It is generally accepted that free intracellular iron catalyzes lipid peroxidation during ferroptosis [27].…”

Section: Effect Of Iron Accumulation and Lipid Peroxidation On Ferroptosismentioning

confidence: 99%

“…Apoptotic bodies are engulfed by macrophages, resulting in an antiinflammatory process. In contrast, ferroptosis is primarily pro-inflammatory due to plasma membrane rupture and the release of intracellular contents [25][26][27]. In a general sense, ferroptosis is a mechanism that protects cellular integrity under normal conditions, but leads to cell death when cellular integrity is compromised, whereas apoptosis represents a suicide mechanism that eliminates certain types of cells from the whole organism at specific time points [28].…”

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confidence: 99%

Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration

2021

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Iron is an essential component in many biological processes in the human body. It is critical for the visual phototransduction cascade in the retina. However, excess iron can be toxic. Iron accumulation and reduced efficiency of intracellular antioxidative defense systems predispose the aging retina to oxidative stress-induced cell death. Age-related macular degeneration (AMD) is characterized by retinal iron accumulation and lipid peroxidation. The mechanisms underlying AMD include oxidative stress-mediated death of retinal pigment epithelium (RPE) cells and subsequent death of retinal photoreceptors. Understanding the mechanism of the disruption of iron and redox homeostasis in the aging retina and AMD is crucial to decipher these mechanisms of cell death and AMD pathogenesis. The mechanisms of retinal cell death in AMD are an area of active investigation; previous studies have proposed several types of cell death as major mechanisms. Ferroptosis, a newly discovered programmed cell death pathway, has been associated with the pathogenesis of several neurodegenerative diseases. Ferroptosis is initiated by lipid peroxidation and is characterized by iron-dependent accumulation. In this review, we provide an overview of the mechanisms of iron accumulation and lipid peroxidation in the aging retina and AMD, with an emphasis on ferroptosis.

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Ferroptosis and Necroptosis in the Kidney

Cited by 156 publications

References 230 publications

Cell death pathways: intricate connections and disease implications

Cell death pathways: intricate connections and disease implications

Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury

Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration

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