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Autophagy Sep 2021Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which is controlled by integrated oxidation and antioxidant... (Review)
Review
Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation, which is controlled by integrated oxidation and antioxidant systems. The iron-containing enzyme lipoxygenase is the main promoter of ferroptosis by producing lipid hydroperoxides, and its function relies on the activation of ACSL4-dependent lipid biosynthesis. In contrast, the selenium-containing enzyme GPX4 is currently recognized as a central repressor of ferroptosis, and its activity depends on glutathione produced from the activation of the cystine-glutamate antiporter SLC7A11. Many metabolic (especially involving iron, lipids, and amino acids) and degradation pathways (macroautophagy/autophagy and the ubiquitin-proteasome system) orchestrate the complex ferroptotic response through direct or indirect regulation of iron accumulation or lipid peroxidation. Although the detailed mechanism of membrane injury during ferroptosis remains a mystery, ESCRT III-mediated plasma membrane repair can make cells resistant to ferroptosis. Here, we review the recent rapid progress in understanding the molecular mechanisms of ferroptosis and focus on the epigenetic, transcriptional, and posttranslational regulation of this process. 2ME: beta-mercaptoethanol; α-KG: α-ketoglutarate; ccRCC: clear cell renal cell carcinoma; EMT: epithelial-mesenchymal transition; FAO: fatty acid beta-oxidation; GSH: glutathione; MEFs: mouse embryonic fibroblasts; MUFAs: monounsaturated fatty acids; NO: nitric oxide; NOX: NADPH oxidase; PPP: pentose phosphate pathway; PUFA: polyunsaturated fatty acid; RCD: regulated cell death; RNS: reactive nitrogen species; ROS: reactive oxygen species; RTAs: radical-trapping antioxidants; UPS: ubiquitin-proteasome system; UTR: untranslated region.
Topics: Animals; Autophagy; Ferroptosis; Fibroblasts; Lipid Peroxidation; Mice; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 32804006
DOI: 10.1080/15548627.2020.1810918 -
Cell May 2020Ferroptosis is a regulated form of cell death that occurs when phospholipids with polyunsaturated fatty acyl tails are oxidized in an iron-dependent manner. Research in...
Ferroptosis is a regulated form of cell death that occurs when phospholipids with polyunsaturated fatty acyl tails are oxidized in an iron-dependent manner. Research in recent years has uncovered complex cellular networks that induce and suppress lethal lipid peroxidation. This SnapShot provides an overview of ferroptosis-related pathways, including relevant biomolecules and small-molecule modulators regulating them.
Topics: Cell Death; Ferroptosis; Humans; Iron; Lipid Peroxidation; Oxidation-Reduction; Phospholipids
PubMed: 32470402
DOI: 10.1016/j.cell.2020.04.039 -
Inflammopharmacology Jun 2020Selenium is an essential immunonutrient which holds the human's metabolic activity with its chemical bonds. The organic forms of selenium naturally present in human body... (Review)
Review
Selenium is an essential immunonutrient which holds the human's metabolic activity with its chemical bonds. The organic forms of selenium naturally present in human body are selenocysteine and selenoproteins. These forms have a unique way of synthesis and translational coding. Selenoproteins act as antioxidant warriors for thyroid regulation, male-fertility enhancement, and anti-inflammatory actions. They also participate indirectly in the mechanism of wound healing as oxidative stress reducers. Glutathione peroxidase (GPX) is the major selenoprotein present in the human body, which assists in the control of excessive production of free radical at the site of inflammation. Other than GPX, other selenoproteins include selenoprotein-S that regulates the inflammatory cytokines and selenoprotein-P that serves as an inducer of homeostasis. Previously, reports were mainly focused on the cellular and molecular mechanism of wound healing with reference to various animal models and cell lines. In this review, the role of selenium and its possible routes in translational decoding of selenocysteine, synthesis of selenoproteins, systemic action of selenoproteins and their indirect assimilation in the process of wound healing are explained in detail. Some of the selenium containing compounds which can acts as cancer preventive and therapeutics are also discussed. These compounds directly or indirectly exhibit antioxidant properties which can sustain the intracellular redox status and these activities protect the healthy cells from reactive oxygen species induced oxidative damage. Although the review covers the importance of selenium/selenoproteins in wound healing process, still some unresolved mystery persists which may be resolved in near future.
Topics: Animals; Antioxidants; Humans; Inflammation; Oxidation-Reduction; Reactive Oxygen Species; Selenium; Selenoproteins
PubMed: 32144521
DOI: 10.1007/s10787-020-00690-x -
Molecules (Basel, Switzerland) Nov 2023This review presents a description of the available data from the literature on the electrochemical properties of flavonoids. The emphasis has been placed on the... (Review)
Review
This review presents a description of the available data from the literature on the electrochemical properties of flavonoids. The emphasis has been placed on the mechanism of oxidation processes and an attempt was made to find a general relation between the observed reaction paths and the structure of flavonoids. Regardless of the solvent used, three potential regions related to flavonoid structures are characteristic of the occurrence of their electrochemical oxidation. The potential values depend on the solvent used. In the less positive potential region, flavonoids, which have an dihydroxy moiety, are reversibly oxidized to corresponding -quinones. The -quinones, if they possess a C3 hydroxyl group, react with water to form a benzofuranone derivative (). In the second potential region, () is irreversibly oxidized. In this potential region, some flavonoids without an dihydroxy moiety can also be oxidized to the corresponding -quinone methides. The oxidation of the hydroxyl groups located in ring A, which are not in the position, occurs in the third potential region at the most positive values. Some discrepancies in the reported reaction mechanisms have been indicated, and this is a good starting point for further investigations.
Topics: Flavonoids; Electrochemistry; Oxidation-Reduction; Solvents
PubMed: 38005343
DOI: 10.3390/molecules28227618 -
Angewandte Chemie (International Ed. in... Dec 2022The Wacker reaction is the oxidation of olefins to ketones and typically requires expensive and scarce palladium catalysts in the presence of an additional copper... (Review)
Review
The Wacker reaction is the oxidation of olefins to ketones and typically requires expensive and scarce palladium catalysts in the presence of an additional copper co-catalyst under harsh conditions (acidic media, high pressure of air/dioxygen, elevated temperatures). Such a transformation is relevant for industry, as shown by the synthesis of acetaldehyde from ethylene as well as for fine-chemicals, because of the versatility of a carbonyl group placed at specific positions. In this regard, many contributions have focused on controlling the chemo- and regioselectivity of the olefin oxidation by means of well-defined palladium catalysts under different sets of reaction conditions. However, the development of Wacker-type processes that avoid the use of palladium catalysts has just emerged in the last few years, thereby paving the way for the generation of more sustainable procedures, including milder reaction conditions and green chemistry technologies. In this Minireview, we discuss the development of new catalytic processes that utilize more benign catalysts and sustainable reaction conditions.
Topics: Palladium; Alkenes; Catalysis; Ketones; Oxidation-Reduction
PubMed: 36164675
DOI: 10.1002/anie.202211016 -
Trends in Pharmacological Sciences Jan 2021The recent emergence of oxidation state selective probes of cellular iron has produced a more nuanced understanding of how cells utilize this crucial nutrient to empower... (Review)
Review
The recent emergence of oxidation state selective probes of cellular iron has produced a more nuanced understanding of how cells utilize this crucial nutrient to empower enzyme function, and also how labile ferrous iron contributes to iron-dependent cell death (ferroptosis) and other disease pathologies including cancer, bacterial infections, and neurodegeneration. These findings, viewed in light of the Fenton chemistry promoted by ferrous iron, suggest a new category of therapeutics exhibiting ferrous iron-dependent pharmacology. While still in its infancy, this nascent field draws inspiration from the remarkable activity and tremendous clinical impact of the antimalarial artemisinin. Here, we review recent insights into the role of labile ferrous iron in biology and disease, and describe new therapeutic approaches designed to exploit this divalent transition metal.
Topics: Cell Death; Ferroptosis; Iron; Oxidation-Reduction
PubMed: 33261861
DOI: 10.1016/j.tips.2020.11.003 -
Current Opinion in Gastroenterology Mar 2023Carnitine is an essential micronutrient that transfer long-chain fatty acids from the cytoplasm into the mitochondrial matrix for the β-oxidation. Carnitine is also... (Review)
Review
PURPOSE OF REVIEW
Carnitine is an essential micronutrient that transfer long-chain fatty acids from the cytoplasm into the mitochondrial matrix for the β-oxidation. Carnitine is also needed for the mitochondrial efflux of acyl groups in the cases wherein substrate oxidation exceeds energy demands.
RECENT FINDINGS
Carnitine deficiency can affect the oxidation of free fatty acids in the mitochondria resulting in the aggregation of lipids in the cytoplasm instead of entering the citric acid cycle. The aggregation leads a lack of energy, acetyl coenzyme A accumulation in the mitochondria and cytotoxic production.
SUMMARY
Carnitine and its derivatives show great clinical therapeutic effect without significant side effects.
Topics: Humans; Carnitine; Fatty Acids; Oxidation-Reduction; Fatigue
PubMed: 36821461
DOI: 10.1097/MOG.0000000000000906 -
Plant Physiology May 2021
Topics: Oxidation-Reduction; Plant Physiological Phenomena; Plants
PubMed: 33710325
DOI: 10.1093/plphys/kiab103 -
The FEBS Journal Dec 2022Oxidoreductases catalyze oxidation-reduction reactions and comprise a very large and diverse group of enzymes, which can be subclassified depending on the catalytic... (Review)
Review
Oxidoreductases catalyze oxidation-reduction reactions and comprise a very large and diverse group of enzymes, which can be subclassified depending on the catalytic mechanisms of the enzymes. One of the most prominent oxidative modifications in proteins is carbonylation, which involves the formation of aldehyde and keto groups in the side chain of lysines. This modification can alter the local macromolecular structure of proteins, thereby regulating their function, stability, and/or localization, as well as the nature of any protein-protein and/or protein-nucleic acid interactions. In this review, we focus on copper-dependent amine oxidases, which catalyze oxidative deamination of amines to aldehydes. In particular, we discuss oxidation reactions that involve lysine residues and that are regulated by members of the lysyl oxidase (LOX) family of proteins. We summarize what is known about the newly identified substrates and how this posttranslational modification regulates protein function in different contexts.
Topics: Lysine; Protein-Lysine 6-Oxidase; Amines; Oxidation-Reduction; Protein Processing, Post-Translational
PubMed: 34535954
DOI: 10.1111/febs.16205 -
Molecular Aspects of Medicine Oct 2020Iron plays an essential role in normal biological processes: The generation of cellular energy, oxygen transport, DNA synthesis and repair are all processes that require... (Review)
Review
Iron plays an essential role in normal biological processes: The generation of cellular energy, oxygen transport, DNA synthesis and repair are all processes that require iron-coordinated proteins, either as elemental iron, heme or iron-sulfur clusters. As a transition metal with two major biological oxidation states, iron is also a critical intermediate in the generation of reactive oxygen species that can damage cellular structures and contribute to both aging and cancer. In this review, we focus on experimental and epidemiologic evidence that links iron and cancer, as well as strategies that have been proposed to either reduce or increase cellular iron for cancer therapy.
Topics: Aging; Humans; Iron; Neoplasms; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 32340745
DOI: 10.1016/j.mam.2020.100860