The Multifaceted Regulation of Mitochondria in Ferroptosis

Wu, Hao; Wang, Fengli; Ta, Na; Zhang, Ting; Gao, Weihua

doi:10.3390/life11030222

Cited by 69 publications

(66 citation statements)

References 220 publications

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“…Singlet oxygen species produced by PDT can oxidize intracellular LDs to form lipid oxide or lipid peroxide [50]. The intracellular lipid peroxidation could initiate cellular ferroptosis, which can induce mitochondrial morphology disruption and depolarization in this process [51]. This may be the mitochondrial damage mechanism of TPE-Py-OH stored in LDs.…”

Section: In Vitro Long-term Tracking and Pdt Of Tpe-py-ohmentioning

confidence: 99%

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting

et al. 2022

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Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen species damage is a promising strategy to enhance the effectiveness of PDT. In this paper, a new PS, 1-[2-hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl)styryl]pyridinium bromide (TPE-Py-OH) of tetraphenylethylene derivative with AIE feature was designed and synthesized for PDT. The TPE-Py-OH can not only simultaneously target lipid droplets and mitochondria, but also stay in cells for a long period (more than 7 days). Taking advantage of the long retention ability of TPE-Py-OH in tumor, the PDT effect of TPE-Py-OH can be activated through multiple irradiations after one injection, which provides a specific multiple light-activated PDT effect. We believe that this AIE-active PS will be promising for the tracking and photodynamic ablation of HCC with sustained effectiveness.

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Section: In Vitro Long-term Tracking and Pdt Of Tpe-py-ohmentioning

confidence: 99%

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting

et al. 2022

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“…Previous ndings have showed that the decline of mitochondrial membrane potential, the obvious shrinkage of mitochondrial morphology and the increase of membrane density are typical features of ferroptosis [20,21]. The results of the TEM illustrated that radiation led to decreased volume of mitochondria and increase of mitochondrial membrane density [22].…”

Section: Ferroptosis Inhibitor Protected Mitochondrial Membrane From Radiation-induced Injurymentioning

confidence: 90%

Activation of The P62-Keap1-NRF2 Pathway Protects Against Ferroptosis in Radiation-Induced Lung Injury

Chen

Yuan

et al. 2021

Preprint

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Background Radiation-induced lung injury (RILI) is one of the most common, serious and dose-limiting complications of thoracic radiotherapy. A primary reason for this is the radiation-induced cell death. Ferroptosis is a recently recognized form of regulated cell death, characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). The ROS induced by irradiation might be the original trigger of ferroptosis in RILI. Furthermore, activation of the P62-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (NRF2) pathway has been shown to exert a protective effect, blunting ferroptosis. Therefore, this study aims to explore the protective effect of the P62-Keap1-NRF2 pathway against radiation-induced ferroptosis in alveolar epithelial cells. Results Firstly, our results demonstrated that radiation induced ferroptosis in vitro RILI cell model, which could be significantly reduced by Ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis. Then, we found that overexpression of P62 interacted with Keap1 to promote NRF2 translocation into the nucleus and upregulation its target proteins quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1) and ferritin heavy chain 1 (FTH1). Conclusion Collectively, the activation of the P62-Keap1-NRF2 pathway prevents radiation-induced ferroptosis in RILI cells, providing a theoretical basis for further research to find a potential approach for RILI therapy.

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“…Recently, this aspect has been significantly actualized in connection with identifying the mitochondriadependent ferroptosis as a new pathway of cell death [39]. A characteristic feature of ferroptosis is iron-dependent lipid peroxidation, which mainly occurs in mitochondrial membranes [39,40]. Excessive free iron is commonly eliminated by iron chelators.…”

Section: Discussionmentioning

confidence: 99%

New Properties and Mitochondrial Targets of Polyphenol Agrimoniin as a Natural Anticancer and Preventive Agent

2021

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Agrimoniin is a polyphenol from the group of tannins with antioxidant and anticancer activities. It is assumed that the anticancer action of agrimoniin is associated with the activation of mitochondria-dependent apoptosis, but its mitochondrial targets have not been estimated. We examined the direct influence of agrimoniin on different mitochondrial functions, including the induction of the mitochondrial permeability transition pore (MPTP) as the primary mechanism of mitochondria-dependent apoptosis. Agrimoniin was isolated from Agrimonia pilosa Ledeb by multistep purification. The content of agrimoniin in the resulting substance reached 80%, as determined by NMR spectroscopy. The cytotoxic effect of purified agrimoniin was confirmed on the cultures of K562 and HeLa cancer cells by the MTT assay. When tested on isolated rat liver mitochondria, agrimoniin at a low concentration (10 µM) induced the low-amplitude swelling, which was inhibited by the MPTP inhibitors ADP and cyclosporine A, activated the opening of MPTP by calcium ions and stimulated the respiration supported by succinate oxidation. Also, agrimoniin reduced the electron acceptor DCPIP in a concentration-dependent manner and chelated iron ions. Owing to all these properties, agrimoniin can stimulate apoptosis or activate mitochondrial functions, which can be helpful in the prevention and elimination of stagnant pathological states.

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The Multifaceted Regulation of Mitochondria in Ferroptosis

Cited by 69 publications

References 220 publications

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting

Activation of The P62-Keap1-NRF2 Pathway Protects Against Ferroptosis in Radiation-Induced Lung Injury

New Properties and Mitochondrial Targets of Polyphenol Agrimoniin as a Natural Anticancer and Preventive Agent

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