Mitochondria regulation in ferroptosis

European Journal of Cell Biology, Год журнала: 2019, Номер 99(1), С. 151058 - 151058

Опубликована: Ноя. 15, 2019

Язык: Английский

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Chaperone-mediated autophagy is involved in the execution of ferroptosis

Proceedings of the National Academy of Sciences, Год журнала: 2019, Номер 116(8), С. 2996 - 3005

Опубликована: Фев. 4, 2019

Significance This study reveals a common regulatory mechanism mediated by HSP90 that is shared necroptosis and ferroptosis, two necrotic cell death mechanisms have previously had no known mechanistic connections. Furthermore, this demonstrates the involvement of chaperone-mediated autophagy in execution ferroptosis. Given role as an important chaperone involved major human maladies ranging from neurodegenerations to cancers, our work further implicates roles ferroptosis diseases.

Язык: Английский

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Cellular degradation systems in ferroptosis

Cell Death and Differentiation, Год журнала: 2021, Номер 28(4), С. 1135 - 1148

Опубликована: Янв. 18, 2021

Язык: Английский

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Signaling pathways and defense mechanisms of ferroptosis

FEBS Journal, Год журнала: 2021, Номер 289(22), С. 7038 - 7050

Опубликована: Июнь 6, 2021

As a type of lytic cell death driven by unrestricted lipid peroxidation and subsequent plasma membrane damage, ferroptosis occurs develops because sophisticated signals regulatory mechanisms. The reactive oxygen species (ROS) used to initiate come from variety sources, including iron‐mediated Fenton reactions, mitochondrial ROS, membrane‐associated ROS the NOX protein family. Polyunsaturated fatty acid‐containing phospholipids are main substrates in ferroptosis, which is positively regulated enzymes, such as ACSL4, LPCAT3, ALOXs, or POR. Selective activation autophagic degradation pathways promotes increasing iron accumulation cause peroxidation. In contrast, system xc – ‐glutathione–GPX4 axis plays central role limiting peroxidation, although other antioxidants (such coenzyme Q10 tetrahydrobiopterin) can also inhibit ferroptosis. A nuclear mechanism defense against NFE2L2‐dependent antioxidant response transcriptionally upregulating expression cytoprotective genes. Additionally, damage caused ferroptotic stimulus be repaired ESCRT‐III‐dependent scission machinery. this review, we summarize recent progress understanding signaling mechanisms

Язык: Английский

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

Cells, Год журнала: 2020, Номер 9(6), С. 1505 - 1505

Опубликована: Июнь 20, 2020

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

Язык: Английский

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Mitochondria ROS and mitophagy in acute kidney injury

Autophagy, Год журнала: 2022, Номер 19(2), С. 401 - 414

Опубликована: Июнь 9, 2022

Mitophagy is an essential mitochondrial quality control mechanism that eliminates damaged mitochondria and the production of reactive oxygen species (ROS). The relationship between oxidative stress, ROS mitophagy are intimately interwoven, these processes all involved in various pathological conditions acute kidney injury (AKI). elimination through mammals a complicated process which involves several pathways. Furthermore, interplay different types cell death, such as apoptosis, pyroptosis ferroptosis unclear. Here we will review recent advances our understanding mitophagy, pathways, relevance pathogenesis AKI.Abbreviations: AKI: injury; AMBRA1: autophagy beclin 1 regulator 1; ATP: adenosine triphosphate; BAK1: BCL2 antagonist/killer BAX: associated X, apoptosis regulator; BCL2: BECN1: BH3: homology domain 3; BNIP3: interacting protein BNIP3L/NIX: 3 like; CASP1: caspase CAT: catalase; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CI-AKI: contrast-induced CISD1: CDGSH iron sulfur CL: cardiolipin; CNP: 2',3'-cyclic nucleotide 3'-phosphodiesterase; DNM1L/DRP1: dynamin E3: enzyme ETC: electron transport chain; FA: folic acid; FUNDC1: FUN14 containing G3P: glycerol-3-phosphate; G6PD: glucose-6-phosphate dehydrogenase; GPX: glutathione peroxidase; GSH: glutathione; GSK3B: glycogen synthase kinase beta; GSR: glutathione-disulfide reductase; HIF1A: hypoxia inducible factor subunit alpha; HUWE1: HECT, UBA WWE IL1B: interleukin IMM: inner membrane; IPC: ischemic preconditioning; IRI: ischemia-reperfusion LIR: LC3-interacting region; LPS: lipopolysaccharide; MA: malate-aspartate; MPT: permeability transition; MUL1: E3 ubiquitin ligase mtROS: ROS; NLR: NOD-like receptor; NLRP3: NLR family pyrin NOX: NADPH oxidase; OGD-R: oxygen-glucose deprivation-reperfusion; OMM: outer OPA1: OPA1 like GTPase; OXPHOS: phosphorylation; PARL: presenilin rhomboid PINK1: PTEN induced PLSCR3: phospholipid scramblase PMP: peptidase, processing; PRDX: peroxiredoxin; PRKN: parkin RBR ligase; RPTC: rat proximal tubular cells; ROS: species; SLC7A11/xCT: solute carrier 7 member 11; SOD: superoxide dismutase; SOR: SQSTM1/p62: sequestosome TCA: tricarboxylic TIMM: translocase TOMM: TXN: thioredoxin; VDAC: voltage dependent anion channel; VCP: valosin protein.

Язык: Английский

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Oxidative Damage and Antioxidant Defense in Ferroptosis

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Сен. 17, 2020

Many new types of regulated cell death have been recently implicated in human health and disease. These deaths different morphological, genetic, biochemical, functional hallmarks. Ferroptosis was originally described as a carcinogenic RAS-dependent non-apoptotic death, is now defined type necrosis characterized by iron accumulation, lipid peroxidation, the release damage-associated molecular patterns (DAMPs). Multiple oxidative antioxidant systems, acting together autophagy machinery, shape process peroxidation during ferroptosis. In particular, production reactive oxygen species (ROS) that depends on activity NADPH oxidases (NOXs) mitochondrial respiratory chain promotes lipoxygenase (ALOX) or cytochrome P450 reductase (POR). contrast, glutathione (GSH), coenzyme Q10 (CoQ10), tetrahydrobiopterin (BH4) system limits damage processes are further transcriptionally nuclear factor, erythroid 2-like 2 (NFE2L2/NRF2), whereas membrane repair ferroptotic requires activation endosomal sorting complexes required for transport (ESCRT)-III. A understanding function ferroptosis may provide precise treatment strategies

Язык: Английский

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Mitochondrial regulation of ferroptosis

The Journal of Cell Biology, Год журнала: 2021, Номер 220(9)

Опубликована: Июль 30, 2021

Ferroptosis is a form of iron-dependent regulated cell death driven by uncontrolled lipid peroxidation. Mitochondria are double-membrane organelles that have essential roles in energy production, cellular metabolism, and regulation. However, their role ferroptosis has been unclear somewhat controversial. In this Perspective, I summarize the diverse metabolic processes mitochondria actively drive ferroptosis, discuss recently discovered mitochondria-localized defense systems detoxify mitochondrial peroxides protect against present new evidence for regulating outline outstanding questions on fascinating topic future investigations. An in-depth understanding functions will important implications both fundamental biology disease treatment.

Язык: Английский

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Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration

Frontiers in Neuroscience, Год журнала: 2018, Номер 12

Опубликована: Июль 10, 2018

Ferroptosis is a newly described form of regulated cell death, distinct from apoptosis, necroptosis and other forms death. induced by disruption glutathione synthesis or inhibition peroxidase 4, exacerbated iron, prevented radical scavengers such as ferrostatin-1, liproxstatin-1 endogenous vitamin E. terminates with mitochondrial dysfunction toxic lipid peroxidation. Although conclusive identification ferroptosis in vivo challenging, several salient very well established features neurodegenerative diseases are consistent ferroptosis, including peroxidation, iron dysregulation. Accordingly, interest the role neurodegeneration escalating specific evidence rapidly emerging. One aspect that has thus far received little attention antioxidant transcription factor nuclear erythroid 2-related 2 (Nrf2). This regulates hundreds genes, which many either directly indirectly involved modulating metabolism glutathione, lipids, function. potentially positions Nrf2 key deterministic component onset outcomes ferroptotic stress. The minimal direct currently available this indicates may be critical for protection against ferroptosis. In contrast, abundant demonstrates enhancing signaling potently neuroprotective models neurodegeneration, although exact mechanism achieved unclear. Further studies required to determine extent effects activation involve prevention

Язык: Английский

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Iron and Cancer

Annual Review of Nutrition, Год журнала: 2018, Номер 38(1), С. 97 - 125

Опубликована: Авг. 21, 2018

This review explores the multifaceted role that iron has in cancer biology. Epidemiological studies have demonstrated an association between excess and increased incidence risk, while experimental implicated initiation, tumor growth, metastasis. The roles of proliferation, metabolism, metastasis underpin with growth progression. Cancer cells exhibit iron-seeking phenotype achieved through dysregulation metabolic proteins. These changes are mediated, at least part, by oncogenes suppressors. dependence on implications a number cell death pathways, including ferroptosis, iron-dependent form death. Uniquely, both depletion can be utilized anticancer therapies. Investigating efficacy these therapeutic approaches is area active research promises substantial clinical impact.

Язык: Английский

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