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      Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis

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          Abstract

          Reactive oxygen species- (ROS-) induced lipid peroxidation plays a critical role in cell death including apoptosis, autophagy, and ferroptosis. This fundamental and conserved mechanism is based on an excess of ROS which attacks biomembranes, propagates lipid peroxidation chain reactions, and subsequently induces different types of cell death. A highly evolved sophisticated antioxidant system exists that acts to protect the cells from oxidative damage. In this review, we discussed how ROS propagate lipid peroxidation chain reactions and how the products of lipid peroxidation initiate apoptosis and autophagy in current models. We also discussed the mechanism of lipid peroxidation during ferroptosis, and we summarized lipid peroxidation in pathological conditions of critical illness. We aim to bring a more global and integrative sight to know how different ROS-induced lipid peroxidation occurs among apoptosis, autophagy, and ferroptosis.

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          Most cited references110

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          Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis.

          Enigmatic lipid peroxidation products have been claimed as the proximate executioners of ferroptosis-a specialized death program triggered by insufficiency of glutathione peroxidase 4 (GPX4). Using quantitative redox lipidomics, reverse genetics, bioinformatics and systems biology, we discovered that ferroptosis involves a highly organized oxygenation center, wherein oxidation in endoplasmic-reticulum-associated compartments occurs on only one class of phospholipids (phosphatidylethanolamines (PEs)) and is specific toward two fatty acyls-arachidonoyl (AA) and adrenoyl (AdA). Suppression of AA or AdA esterification into PE by genetic or pharmacological inhibition of acyl-CoA synthase 4 (ACSL4) acts as a specific antiferroptotic rescue pathway. Lipoxygenase (LOX) generates doubly and triply-oxygenated (15-hydroperoxy)-diacylated PE species, which act as death signals, and tocopherols and tocotrienols (vitamin E) suppress LOX and protect against ferroptosis, suggesting a homeostatic physiological role for vitamin E. This oxidative PE death pathway may also represent a target for drug discovery.
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            Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy

            Autophagy, the process by which proteins and organelles are sequestered in double-membrane structures called autophagosomes and delivered to lysosomes for degradation, is critical in diseases such as cancer and neurodegeneration 1,2 . Much of our understanding of this process has emerged from analysis of bulk cytoplasmic autophagy, but our understanding of how specific cargo including organelles, proteins, or intracellular pathogens are targeted for selective autophagy is limited 3 . We employed quantitative proteomics to identify a cohort of novel and known autophagosome-enriched proteins, including cargo receptors. Like known cargo receptors, NCOA4 was highly enriched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into autophagosomes. Unbiased identification of NCOA4-associated proteins revealed ferritin heavy and light chains, components of an iron-filled cage structure that protects cells from reactive iron species 4 but is degraded via autophagy to release iron 5,6 through an unknown mechanism. We found that delivery of ferritin to lysosomes required NCOA4, and an inability of NCOA4-deficient cells to degrade ferritin leads to decreased bioavailable intracellular iron. This work identifies NCOA4 as a selective cargo receptor for autophagic turnover of ferritin (ferritinophagy) critical for iron homeostasis and provides a resource for further dissection of autophagosomal cargo-receptor connectivity.
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              Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

              Wang et al. review the dual role of superoxide dismutases in controlling reactive oxygen species (ROS) damage and regulating ROS signaling across model systems as well as their involvement in human diseases.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2019
                13 October 2019
                : 2019
                : 5080843
                Affiliations
                1Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei Province, China
                2Center of Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, 15223 PA, USA
                Author notes

                Academic Editor: Victor M. Victor

                Author information
                https://orcid.org/0000-0002-3873-9607
                Article
                10.1155/2019/5080843
                6815535
                31737171
                8a9521a7-e73b-403c-a501-8982330793fc
                Copyright © 2019 Lian-Jiu Su et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 April 2019
                : 15 July 2019
                : 20 August 2019
                Funding
                Funded by: Health Commission of Hubei Province
                Award ID: WJ2017Z008
                Funded by: Hubei Province Technology and Innovation Project
                Award ID: 2017AHB044
                Funded by: National Natural Science Foundation of China
                Award ID: 81560131
                Award ID: 81772046
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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