Copper homeostasis and cuproptosis in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 23, 2022

As an essential micronutrient, copper is required for a wide range of physiological processes in virtually all cell types. Because the accumulation intracellular can induce oxidative stress and perturbing cellular function, homeostasis tightly regulated. Recent studies identified novel copper-dependent form death called cuproptosis, which distinct from other known pathways underlying death. Cuproptosis occurs via binding to lipoylated enzymes tricarboxylic acid (TCA) cycle, leads subsequent protein aggregation, proteotoxic stress, ultimately Here, we summarize our current knowledge regarding metabolism, copper-related disease, characteristics mechanisms that regulate cuproptosis. In addition, discuss implications cuproptosis pathogenesis various disease conditions, including Wilson's neurodegenerative diseases, cancer, therapeutic potential targeting

Language: Английский

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Targeting ferroptosis opens new avenues for the development of novel therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 21, 2023

Abstract Ferroptosis is an iron-dependent form of regulated cell death with distinct characteristics, including altered iron homeostasis, reduced defense against oxidative stress, and abnormal lipid peroxidation. Recent studies have provided compelling evidence supporting the notion that ferroptosis plays a key pathogenic role in many diseases such as various cancer types, neurodegenerative disease, involving tissue and/or organ injury, inflammatory infectious diseases. Although precise regulatory networks underlie are largely unknown, particularly respect to initiation progression diseases, recognized bona fide target for further development treatment prevention strategies. Over past decade, considerable progress has been made developing pharmacological agonists antagonists these ferroptosis-related conditions. Here, we provide detailed overview our current knowledge regarding ferroptosis, its pathological roles, regulation during disease progression. Focusing on use chemical tools preclinical studies, also summarize recent advances targeting across growing spectrum ferroptosis-associated Finally, discuss new challenges opportunities potential strategy treating

Language: Английский

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Endoplasmic reticulum stress-mediated cell death in liver injury

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(12)

Published: Dec. 19, 2022

The endoplasmic reticulum is an important intracellular organelle that plays role in maintaining cellular homeostasis. Endoplasmic stress (ERS) and unfolded protein response (UPR) are induced when the body exposed to adverse external stimuli. It has been established ERS can induce different cell death modes, including autophagy, apoptosis, ferroptosis, pyroptosis, through three major transmembrane receptors on ER membrane, inositol requirement enzyme 1α, kinase-like kinase activating transcription factor 6. These modes of play occurrence development various diseases, such as neurodegenerative inflammation, metabolic liver injury. As largest organ, rich enzymes, carries out functions metabolism secretion, body's main site synthesis. Accordingly, a well-developed system present hepatocytes help perform its physiological functions. Current evidence suggests closely related stages injury, caused by may be key In addition, increasing modulating great potential for treating This article provided comprehensive overview relationship between four types death. Moreover, we discussed mechanism UPR injuries their therapeutic strategies.

Language: Английский

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Mitochondria-associated programmed cell death as a therapeutic target for age-related disease

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1595 - 1619

Published: Aug. 23, 2023

Abstract Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed death. Thus, dysfunctional eventually lead or contribute to age-related diseases, such neurodegenerative, cardiovascular diseases. mitochondrion-associated death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli maintain homeostasis via mitohormesis, unfolded protein response, mitophagy. The also presents details on forms mitochondria-associated death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, paraptosis, highlights their involvement disease pathogenesis, collectively suggesting directions further research.

Language: Английский

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Fighting age-related orthopedic diseases: focusing on ferroptosis

Bone Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: March 1, 2023

Abstract Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid the biosynthesis compounds with antioxidant activities, glutathione. In past 10 years, increasing evidence has indicated potentially strong relationship between ferroptosis onset progression age-related orthopedic diseases, such as osteoporosis osteoarthritis. Therefore, in-depth knowledge regulatory mechanisms in diseases may help improve disease treatment prevention. This review provides an overview recent research on its influences bone cartilage homeostasis. begins brief systemic metabolism ferroptosis, particularly potential ferroptosis. presents discussion role promotion loss degradation inhibition osteogenesis. Finally, it focuses future targeting treat intention inspiring further clinical development therapeutic strategies.

Language: Английский

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The structure of erastin-bound xCT–4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis

Cell Research, Journal Year: 2022, Volume and Issue: 32(7), P. 687 - 690

Published: March 29, 2022

Dear Editor

Language: Английский

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

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Ferroptosis in health and disease

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103211 - 103211

Published: May 30, 2024

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark ferroptosis uncontrolled overwhelming peroxidation polyunsaturated fatty acids contained membrane phospholipids, which eventually leads to rupture the plasma membrane. unique that it essentially spontaneous, uncatalyzed chemical process based on perturbed iron redox homeostasis contributing process, but nonetheless modulated by many metabolic nodes impinge cells' susceptibility ferroptosis. Among affecting sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets treatment numerous currently incurable diseases. Herein, current members Germany-wide research consortium focusing research, well key external experts who made seminal contributions this rapidly growing exciting field gathered provide comprehensive, state-of-the-art review Specific topics include: basic mechanisms, vivo relevance, specialized methodologies, tools, potential contribution disease etiopathology progression. We hope article will not only established scientists newcomers with an overview multiple facets ferroptosis, also encourage additional efforts characterize further molecular pathways modulating ultimate goal develop novel pharmacotherapies tackle associated - or caused

Language: Английский

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Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(12), P. 2111 - 2130

Published: Dec. 14, 2023

Abstract Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading fatal diseases. Senescent cells are main driver fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report cellular senescence, multiple types in mice humans characterized by the accumulation iron. We show vascular hemolytic injuries efficient triggering iron accumulation, which turn cause senescence promote fibrosis. Notably, find senescent persistently accumulate iron, even when surge extracellular has subdued. Indeed, under conditions exposed different senescence-inducing insults abundant ferritin-bound mostly within lysosomes, present high levels labile fuels generation reactive oxygen species SASP. Finally, demonstrate detection magnetic resonance imaging might allow non-invasive assessment burden kidneys patients with renal Our findings suggest plays central role fibrosis, initiating events may be independent identify metabolism potential therapeutic target for

Language: Английский

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N6-Methyladenosine-modified circSAV1 triggers ferroptosis in COPD through recruiting YTHDF1 to facilitate the translation of IREB2

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(5), P. 1293 - 1304

Published: Feb. 24, 2023

Language: Английский

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