Mitochondria regulation in ferroptosis

Wang, Hai; Liu, Can; Zhao, Yongxin; Gao, Ge

doi:10.1016/j.ejcb.2019.151058

Cited by 382 publications

(272 citation statements)

References 124 publications

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“…Transmission electron microscopy (TEM) reveals the presence of small mitochondria with increased mitochondrial membrane density and vanishing of mitochondrial cristae. The cell membrane remains intact and the nucleus shows a normal size, without chromatin concentration [98,99]. This table lists several genes, proteins, microRNAs, and lncRNAs, acting as modulators of the ferroptosis process.…”

Section: Ferroptosis and Cancermentioning

confidence: 99%

Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Battaglia

Chirillo

Aversa

et al. 2020

Cells

315

232

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Ferroptosis is a new type of oxidative regulated cell death (RCD) driven by iron-dependent lipid peroxidation. As major sites of iron utilization and master regulators of oxidative metabolism, mitochondria are the main source of reactive oxygen species (ROS) and, thus, play a role in this type of RCD. Ferroptosis is, indeed, associated with severe damage in mitochondrial morphology, bioenergetics, and metabolism. Furthermore, dysregulation of mitochondrial metabolism is considered a biochemical feature of neurodegenerative diseases linked to ferroptosis. Whether mitochondrial dysfunction can, per se, initiate ferroptosis and whether mitochondrial function in ferroptosis is context-dependent are still under debate. Cancer cells accumulate high levels of iron and ROS to promote their metabolic activity and growth. Of note, cancer cell metabolic rewiring is often associated with acquired sensitivity to ferroptosis. This strongly suggests that ferroptosis may act as an adaptive response to metabolic imbalance and, thus, may constitute a new promising way to eradicate malignant cells. Here, we review the current literature on the role of mitochondria in ferroptosis, and we discuss opportunities to potentially use mitochondria-mediated ferroptosis as a new strategy for cancer therapy.

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Section: Ferroptosis and Cancermentioning

confidence: 99%

Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Battaglia

Chirillo

Aversa

et al. 2020

Cells

315

232

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“…However, once released from the mitochondria into the cytoplasm, upon cristae opening, these pleiotropic proteins convert into apoptosis initiators, pushing the cell toward a deadly end (Snigirevskaya and Komissarchik, 2019). Besides apoptosis, mitochondria are also recognized by regulating other types of cell death such as necroptosis, ferroptosis, pyroptosis, and mitochondrial-mediated necrosis (Baines, 2010;Baker et al, 2014;Marshall and Baines, 2014;Battaglia et al, 2020;Kai et al, 2020;Wang et al, 2020;Wei et al, 2020). Finally, the IM encloses the mitochondrial matrix, where essential reactions take place, such as iron-sulfur cluster assembly (Cardenas et al, 2018;Lill, 2020) or the tricarboxylic acid (TCA) cycle, which feeds electrons to the respiratory chain and provides amino acid precursors (Mailloux et al, 2007;Martínez-Reyes and Chandel, 2020).…”

Section: Introductionmentioning

confidence: 99%

Role of Mitofusins and Mitophagy in Life or Death Decisions

Joaquim

Escobar-Henriques

2020

Front. Cell Dev. Biol.

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Mitochondria entail an incredible dynamism in their morphology, impacting death signaling and selective elimination of the damaged organelles. In turn, by recycling the superfluous or malfunctioning mitochondria, mostly prevalent during aging, mitophagy contributes to maintain a healthy mitochondrial network. Mitofusins locate at the outer mitochondrial membrane and control the plastic behavior of mitochondria, by mediating fusion events. Besides deciding on mitochondrial interconnectivity, mitofusin 2 regulates physical contacts between mitochondria and the endoplasmic reticulum, but also serves as a decisive docking platform for mitophagy and apoptosis effectors. Thus, mitofusins integrate multiple bidirectional inputs from and into mitochondria and ensure proper energetic and metabolic cellular performance. Here, we review the role of mitofusins and mitophagy at the crossroad between life and apoptotic death decisions. Furthermore, we highlight the impact of this interplay on disease, focusing on how mitofusin 2 and mitophagy affect non-alcoholic fatty liver disease.

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“…Furthermore, the GSH/GSSG and GPx4 expression levels should be assessed to examine the suppression of antioxidants during ferroptosis 112 . At last, it is evident to observe condensed mitochondrial membrane with smaller volume, in addition to the reduction or vanishing of mitochondria crista and ruptured outer membrane 55 . It is necessary to integrally conduct ferroptotic assays from distinct aspects for pinpointing the occurrence of this modality.…”

Section: Conclusion and Future Research Perspectivesmentioning

confidence: 96%

“…Intriguingly, it is well exploited that mitochondrial damage may result in inflammasome activation 54 . Emerging evidence implicates that mitochondria are more likely to play a crucial role in the progression of ferroptosis 55 . Whether targeting the mitochondrial metabolic and redox reaction with subsequent intervention on ferroptotic cell death may prevent this excessive inflammasome activation remains to be elucidated.…”

Section: Ferroptosis In Non-cancer Liver Diseasesmentioning

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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Mitochondria regulation in ferroptosis

Cited by 382 publications

References 124 publications

Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Role of Mitofusins and Mitophagy in Life or Death Decisions

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

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