Oxidative stress-dependent frataxin inhibition mediated alcoholic hepatocytotoxicity through ferroptosis

Liu, Jingjing; He, Hui; Wang, Jing; Guo, Xiaoping; Lin, Hongkun; Chen, Huimin; Jiang, Chunjie; Chen, Li; Yao, Ping; Tang, Yuhan

doi:10.1016/j.tox.2020.152584

Cited by 36 publications

(24 citation statements)

References 47 publications

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“…Similarly, some investigations found that dimethyl fumarate has a protective effect on ethanol-induced oxidative injury through activating the Nrf2 pathway and repressing ferroptosis [ 73 ]. Moreover, a recent study implied that ferroptosis was the downstream event of some genes like frataxin to induce liver injury in the context of excessive alcohol exposure [ 75 ].…”

Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

Ferroptosis in liver disease: new insights into disease mechanisms

et al. 2021

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Characterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other well-known cell death. In recent years, ferroptosis has been quickly gaining attention in the field of liver diseases, as the liver is predisposed to oxidative injury and generally, excessive iron accumulation is a primary characteristic of most major liver diseases. In the current review, we first delineate three cellular defense mechanisms against ferroptosis (GPx4 in the mitochondria and cytosol, FSP1 on plasma membrane, and DHODH in mitochondria), along with four canonical modulators of ferroptosis (system Xc−, nuclear factor erythroid 2-related factor 2, p53, and GTP cyclohydrolase-1). Next, we review recent progress of ferroptosis studies delineating molecular mechanisms underlying the pathophysiology of several common liver diseases including ischemia/reperfusion-related injury (IRI), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hemochromatosis (HH), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). Furthermore, we also highlight both challenges and promises that emerged from recent studies that should be addressed and pursued in future investigations before ferroptosis regulation could be adopted as an effective therapeutic target in clinical practice.

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Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

Ferroptosis in liver disease: new insights into disease mechanisms

et al. 2021

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“…frataxin enhanced ethanol-driven ferroptosis, and restoration of the appropriate level of frataxin reduced the sensitivity of liver to ethanol treatment [15].…”

Section: Molecular Mechanisms Of Ferroptosismentioning

confidence: 94%

“…Long-term administration of ethanol to mice reduced the expression of the gene encoding frataxin, leading to the accumulation of ROS and the mitochondrial iron pool in primary hepatocytes. Moreover, deficiency of frataxin enhanced ethanol-driven ferroptosis, and restoration of the appropriate level of frataxin reduced the sensitivity of liver to ethanol treatment [15].…”

Section: Molecular Mechanisms Of Ferroptosismentioning

confidence: 98%

Ferroptosis and Its Modulation by Autophagy in Light of the Pathogenesis of Lysosomal Storage Diseases

Pierzynowska

Rintz

Gaffke

et al. 2021

Cells

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Ferroptosis is one of the recently described types of cell death which is dependent on many factors, including the accumulation of iron and lipid peroxidation. Its induction requires various signaling pathways. Recent discovery of ferroptosis induction pathways stimulated by autophagy, so called autophagy-dependent ferroptosis, put our attention on the role of ferroptosis in lysosomal storage diseases (LSD). Lysosome dysfunction, observed in these diseases, may influence ferroptosis efficiency, with as yet unknown consequences for the function of cells, tissues, and organisms, due to the effects of ferroptosis on physiological and pathological metabolic processes. Modulation of levels of ferrous ions and enhanced oxidative stress, which are primary markers of ferroptosis, are often described as processes associated with the pathology of LSD. Inhibition of autophagy flux and resultant accumulation of autophagosomes in neuronopathic LSD may induce autophagy-dependent ferroptosis, indicating a considerable contribution of this process in neurodegeneration. In this review article, we describe molecular mechanisms of ferroptosis in light of LSD, underlining the modulation of levels of ferroptosis markers in these diseases. Furthermore, we propose a hypothesis about the possible involvement of autophagy-dependent ferroptosis in these disorders.

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“…Studies have shown that ferroptosis inhibitors can significantly alleviate hepatocyte death induced by alcohol ( Gao et al, 2017 ; Liu C.-Y. et al, 2020 ; Liu J. et al, 2020 ; Miyata and Nagy, 2020 ). For instance, ferrostatin-1, a selective inhibitor of ferroptosis, has been demonstrated to reduce alcoholic liver injury in mice ( Suzuki et al, 2002 ).…”

Section: The Role Of Ferroptosis In Liver Diseasesmentioning

confidence: 99%

The Emerging Role of Ferroptosis in Liver Diseases

Chen¹,

Zhu²,

Zang³

et al. 2021

Front. Cell Dev. Biol.

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Ferroptosis is a newly discovered type of cell death mediated by iron-dependent lipid peroxide. The disturbance of iron metabolism, imbalance of the amino acid antioxidant system, and lipid peroxide accumulation are considered distinct fingerprints of ferroptosis. The dysregulation of ferroptosis has been intensively studied in recent years due to its participation in various diseases, including cancer, kidney injury, and neurodegenerative diseases. Notably, increasing evidence indicates that ferroptosis plays different roles in a wide spectrum of liver diseases. On the one hand, inhibiting ferroptosis may counteract the pathophysiological progression of several liver diseases, such as alcoholic liver injury, nonalcoholic steatosis hepatitis and fibrosis. On the other hand, inducing ferroptosis may restrict the emergence of secondary resistance to current medicines, such as sorafenib, for hepatocellular carcinoma (HCC) therapy. Here, we summarize the biological characteristics and regulatory signalling pathways of ferroptosis involved in liver disease. The current available medical agents targeting ferroptosis, including inducers or inhibitors applied in liver diseases, are also reviewed. This work aims to provide new insight into the emerging role of pathogenesis and therapeutic approaches for liver diseases.

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Oxidative stress-dependent frataxin inhibition mediated alcoholic hepatocytotoxicity through ferroptosis

Cited by 36 publications

References 47 publications

Ferroptosis in liver disease: new insights into disease mechanisms

Ferroptosis in liver disease: new insights into disease mechanisms

Ferroptosis and Its Modulation by Autophagy in Light of the Pathogenesis of Lysosomal Storage Diseases

The Emerging Role of Ferroptosis in Liver Diseases

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