The Role of NCOA4-Mediated Ferritinophagy in Health and Disease

Santana-Codina, Naiara; Mancias, Joseph D.

doi:10.3390/ph11040114

Cited by 221 publications

(168 citation statements)

References 100 publications

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“…− are crucial ferroptosis pathway components. 3. Accumulating evidence has addressed that blockage of ferroptosis can mitigate the progression of liver damages of various etiologies.…”

Section: Gpx4 and System X Cmentioning

confidence: 99%

The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?

et al. 2020

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Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system xc− have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.

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“…− are crucial ferroptosis pathway components. 3. Accumulating evidence has addressed that blockage of ferroptosis can mitigate the progression of liver damages of various etiologies.…”

Section: Gpx4 and System X Cmentioning

confidence: 99%

The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?

et al. 2020

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“…In this process, the nuclear receptor coactivator 4 (NCOA4, a selective cargo receptor for the turnover of ferritin) helps to maintain iron homeostasis, contributing to ferritin degradation, thus increasing iron levels and promoting the development of ferroptosis. Autophagy promotes ferroptosis by the degradation of ferritin [58,59].…”

Section: Autophagymentioning

confidence: 99%

Reclassifying Hepatic Cell Death during Liver Damage: Ferroptosis—A Novel Form of Non-Apoptotic Cell Death?

Macías-Rodríguez

Inzaugarat

Ruiz-Margáin

et al. 2020

IJMS

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Ferroptosis has emerged as a new type of cell death in different pathological conditions, including neurological and kidney diseases and, especially, in different types of cancer. The hallmark of this regulated cell death is the presence of iron-driven lipid peroxidation; the activation of key genes related to this process such as glutathione peroxidase-4 (gpx4), acyl-CoA synthetase long-chain family member-4 (acsl4), carbonyl reductase [NADPH] 3 (cbr3), and prostaglandin peroxidase synthase-2 (ptgs2); and morphological changes including shrunken and electron-dense mitochondria. Iron overload in the liver has long been recognized as both a major trigger of liver damage in different diseases, and it is also associated with liver fibrosis. New evidence suggests that ferroptosis might be a novel type of non-apoptotic cell death in several liver diseases including non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), drug-induced liver injury (DILI), viral hepatitis, and hemochromatosis. The interaction between iron-related lipid peroxidation, cellular stress signals, and antioxidant systems plays a pivotal role in the development of this novel type of cell death. In addition, integrated responses from lipidic mediators together with free iron from iron-containing enzymes are essential to understanding this process. The presence of ferroptosis and the exact mechanisms leading to this non-apoptotic type of cell death in the liver remain scarcely elucidated. Recognizing ferroptosis as a novel type of cell death in the liver could lead to the understanding of the complex interaction between different types of cell death, their role in progression of liver fibrosis, the development of new biomarkers, as well as the use of modulators of ferroptosis, allowing improved theranostic approaches in the clinic.

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“…p62, a homolog of plant selective autophagy cargo receptor NBR1, degrades the core circadian clock protein ARNTL, thus facilitating ferroptosis induction. Additionally, Nuclear receptor COactivator 4 (NCOA4) is a selective cargo receptor in mammals that mediates the autophagic degradation of ferritin ("ferritinophagy"), the main iron storage complex [107]. Iron released to the cytosol from ferritin is necessary to generate ROS; thus, ferroptosis sensitivity has recently been shown to be modulated by ferritinophagy [108].…”

Section: Autophagy In the Regulation Of Iron Homeostasismentioning

confidence: 99%

The Role of Selective Protein Degradation in the Regulation of Iron and Sulfur Homeostasis in Plants

Wawrzyńska

Sirko

2020

IJMS

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Plants are able to synthesize all essential metabolites from minerals, water, and light to complete their life cycle. This plasticity comes at a high energy cost, and therefore, plants need to tightly allocate resources in order to control their economy. Being sessile, plants can only adapt to fluctuating environmental conditions, relying on quality control mechanisms. The remodeling of cellular components plays a crucial role, not only in response to stress, but also in normal plant development. Dynamic protein turnover is ensured through regulated protein synthesis and degradation processes. To effectively target a wide range of proteins for degradation, plants utilize two mechanistically-distinct, but largely complementary systems: the 26S proteasome and the autophagy. As both proteasomaland autophagy-mediated protein degradation use ubiquitin as an essential signal of substrate recognition, they share ubiquitin conjugation machinery and downstream ubiquitin recognition modules. Recent progress has been made in understanding the cellular homeostasis of iron and sulfur metabolisms individually, and growing evidence indicates that complex crosstalk exists between iron and sulfur networks. In this review, we highlight the latest publications elucidating the role of selective protein degradation in the control of iron and sulfur metabolism during plant development, as well as environmental stresses. are present at certain concentrations, i.e., when the demand meets the supply. Below such levels, the demand for a nutrient exceeds the supply, so plant growth is ultimately limited by a nutritional deficiency. Conversely, an excess of any nutrient is toxic to plants and also negatively affects plant growth and development. Plants can therefore experience transitions between deficiency or toxicity zones due to changes in the availability of nutrients and growth requirements, but they can return to homeostasis so long as the response is adequate and sufficient. Such adjustments may require time, but they are crucial for plant adaptation. A significant part of this adaptation relies on selective protein degradation (Figure 1). Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 2 of 21 nutrients are present at certain concentrations, i.e., when the demand meets the supply. Below such levels, the demand for a nutrient exceeds the supply, so plant growth is ultimately limited by a nutritional deficiency. Conversely, an excess of any nutrient is toxic to plants and also negatively affects plant growth and development. Plants can therefore experience transitions between deficiency or toxicity zones due to changes in the availability of nutrients and growth requirements, but they can return to homeostasis so long as the response is adequate and sufficient. Such adjustments may require time, but they are crucial for plant adaptation. A significant part of this adaptation relies on selective protein degradation ( Figure 1). Figure 1.Regulation of nutrient deficiency stress by ubiquitination. The plant perceives nutrient deficienc...

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The Role of NCOA4-Mediated Ferritinophagy in Health and Disease

Cited by 221 publications

References 100 publications

The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?

The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?

Reclassifying Hepatic Cell Death during Liver Damage: Ferroptosis—A Novel Form of Non-Apoptotic Cell Death?

The Role of Selective Protein Degradation in the Regulation of Iron and Sulfur Homeostasis in Plants

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