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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Autophagy: Regulator of cell death

Cell Death and Disease, Год журнала: 2023, Номер 14(10)

Опубликована: Окт. 4, 2023

Abstract Autophagy is the process by which cells degrade and recycle proteins organelles to maintain intracellular homeostasis. Generally, autophagy plays a protective role in cells, but disruption of mechanisms or excessive autophagic flux usually leads cell death. Despite recent progress study regulation underlying molecular autophagy, numerous questions remain be answered. How does regulate death? What are fine-tuned regulatory autophagy-dependent death (ADCD) autophagy-mediated (AMCD)? In this article, we highlight different roles discuss six main autophagy-related modalities, with focus on metabolic changes caused endoplasmic reticulum-phagy (ER-phagy)-induced mitophagy ferroptosis. Finally, enhancement treatment diseases offer new perspective based use for functional conversions (including conversion that modalities) clinical tumors.

Язык: Английский

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Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(22), С. 8765 - 8765

Опубликована: Ноя. 20, 2020

Ferroptosis is a type of cell death that was described less than decade ago. It caused by the excess free intracellular iron leads to lipid (hydro) peroxidation. Iron essential as redox metal in several physiological functions. The brain one organs known be affected homeostatic balance disruption. Since 1960s, increased concentration central nervous system has been associated with oxidative stress, oxidation proteins and lipids, death. Here, we review main mechanisms involved process ferroptosis such peroxidation, glutathione peroxidase 4 enzyme activity, metabolism. Moreover, association pathophysiology some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, Huntington’s also addressed.

Язык: Английский

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Programmed Cell Death Tunes Tumor Immunity

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 30, 2022

The demise of cells in various ways enables the body to clear unwanted cells. Studies over years revealed distinctive molecular mechanisms and functional consequences several key cell death pathways. Currently, most intensively investigated programmed (PCD) includes apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis, autophagy, which has been discovered play crucial roles modulating immunosuppressive tumor microenvironment (TME) determining clinical outcomes cancer therapeutic approaches. PCD can dual roles, either pro-tumor or anti-tumor, partly depending on intracellular contents released during process. also regulates enrichment effector regulatory immune cells, thus participating fine-tuning anti-tumor immunity TME. In this review, we focused primarily discussed messengers regulating their intricate crosstalk with response TME, explored immunological consequence its implications future therapy developments.

Язык: Английский

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Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(5), С. 2075 - 2090

Опубликована: Янв. 1, 2022

Ferroptosis and neuroinflammation play crucial roles in Alzheimer's disease (AD) pathophysiology. Forsythoside A (FA), the main constituent of Forsythia suspensa (Thunb.) Vahl., possesses anti-inflammatory, antibacterial, antioxidant, neuroprotective properties. The present study aimed to investigate potential role FA AD neuropathology using male APP/PS1 double transgenic mice, Aβ1-42-exposed N2a cells, erastin-stimulated HT22 LPS-induced BV2 cells. treatment significantly improved mitochondrial function inhibited lipid peroxidation In LPS-stimulated decreased formation pro-inflammatory factors IL-6, IL-1β, NO. ameliorated memory cognitive impairments suppressed Aβ deposition p-tau levels brain. Analyses proteomics, immunohistochemistry, ELISA, western blot revealed that augmented dopaminergic signaling, iron peroxidation, prevented activation IKK/IκB/NF-κB reduced secretion factors, promoted production anti-inflammatory exerted anti-ferroptosis anti-neuroinflammatory effects Nrf2/GPX4 axis played a key these effects. Collectively, results demonstrate protective highlight its therapeutic as drug component for treatment.

Язык: Английский

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Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Язык: Английский

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“Electron Transport Chain Interference” Strategy of Amplified Mild-Photothermal Therapy and Defect-Engineered Multi-Enzymatic Activities for Synergistic Tumor-Personalized Suppression

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(17), С. 9488 - 9507

Опубликована: Март 31, 2023

Arming activatable mild-photothermal therapy (PTT) with the property of relieving tumor thermotolerance holds great promise for overcoming traditional mild PTT limitations such as thermoresistance, insufficient therapeutic effect, and off-target heating. Herein, a mitochondria-targeting, defect-engineered AFCT nanozyme enhanced multi-enzymatic activity was elaborately designed microenvironment (TME)-activatable phototheranostic agent to achieve remarkable anti-tumor via "electron transport chain (ETC) interference synergistic adjuvant therapy". Density functional theory calculations revealed that effect among multi-enzyme active centers endows nanozymes excellent catalytic activity. In TME, open sources H2O2 can be achieved by superoxide dismutase-mimicking nanozymes. response dual stimuli acidity, peroxidase-mimicking not only catalyzes accumulation generate ·OH but also converts loaded 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form strong near-infrared absorption, specifically unlocking photothermal photoacoustic imaging properties. Intriguingly, undesired thermoresistance cells greatly alleviated owing reduced expression heat shock proteins enabled NADH POD-mimicking AFCT-mediated depletion consequent restriction ATP supply. Meanwhile, accumulated facilitate both apoptosis ferroptosis in cells, resulting outcomes combination TME-activated PTT.

Язык: Английский

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ROS induced lipid peroxidation and their role in ferroptosis

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Авг. 1, 2023

Reactive oxygen species (ROS) play a crucial part in the process of cell death, including apoptosis, autophagy, and ferroptosis. ROS involves oxidation lipids generate 4-hydroxynonenal other compounds associated with it. Ferroptosis may be facilitated by lipid peroxidation phospholipid bilayers. In order to offer novel ideas directions for investigation disorders connected these processes, we evaluate function which ultimately leads ferroptosis as well proposed crosstalk mechanisms between types programmed death.

Язык: Английский

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Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview

Life, Год журнала: 2021, Номер 11(4), С. 332 - 332

Опубликована: Апрель 10, 2021

Mitochondria are key intracellular organelles involved not only in the metabolic state of cell, but also several cellular functions, such as proliferation, Calcium signaling, and lipid trafficking. Indeed, these characterized by continuous events fission fusion which contribute to dynamic plasticity their network, strongly influenced mitochondrial contacts with other subcellular organelles. Nevertheless, mitochondria release a major amount reactive oxygen species (ROS) inside eukaryotic cells, reported mediate plethora both physiological pathological growth regulation autophagy, apoptosis, metastasis. Therefore, targeting ROS could be promising strategy overcome hinder development diseases cancer, where malignant possessing higher respect healthy ones, specifically targeted therapeutic treatments. In this review, we collected ultimate findings on blended interplay among shaping, ROS, signaling pathways, order dissection molecular mechanisms pathophysiology possibly improving future approaches.

Язык: Английский

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Targeting ferroptosis in acute kidney injury

Cell Death and Disease, Год журнала: 2022, Номер 13(2)

Опубликована: Фев. 24, 2022

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As form of programmed cell death (PCD), ferroptosis could be considered as process iron accumulation enhanced lipid peroxidation. Recently, the fundamental roles in AKI have attracted much attention. The network mechanism its to chronic disease (CKD) transition complicated multifactorial. Strategies targeting show great potential. Here, we review research progress on participation AKI. We hope that this work will provide clues for further studies

Язык: Английский

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