Cargando…

Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis

Regulated cell death (RCD) has a significant impact on development, tissue homeostasis, and the occurrence of various diseases. Among different forms of RCD, ferroptosis is considered as a type of reactive oxygen species (ROS)-dependent regulated necrosis. ROS can react with polyunsaturated fatty ac...

Descripción completa

Detalles Bibliográficos
Autores principales: Rochette, Luc, Dogon, Geoffrey, Rigal, Eve, Zeller, Marianne, Cottin, Yves, Vergely, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820499/
https://www.ncbi.nlm.nih.gov/pubmed/36613888
http://dx.doi.org/10.3390/ijms24010449
_version_ 1784865479184089088
author Rochette, Luc
Dogon, Geoffrey
Rigal, Eve
Zeller, Marianne
Cottin, Yves
Vergely, Catherine
author_facet Rochette, Luc
Dogon, Geoffrey
Rigal, Eve
Zeller, Marianne
Cottin, Yves
Vergely, Catherine
author_sort Rochette, Luc
collection PubMed
description Regulated cell death (RCD) has a significant impact on development, tissue homeostasis, and the occurrence of various diseases. Among different forms of RCD, ferroptosis is considered as a type of reactive oxygen species (ROS)-dependent regulated necrosis. ROS can react with polyunsaturated fatty acids (PUFAs) of the lipid (L) membrane via the formation of a lipid radical L• and induce lipid peroxidation to form L-ROS. Ferroptosis is triggered by an imbalance between lipid hydroperoxide (LOOH) detoxification and iron-dependent L-ROS accumulation. Intracellular iron accumulation and lipid peroxidation are two central biochemical events leading to ferroptosis. Organelles, including mitochondria and lysosomes are involved in the regulation of iron metabolism and redox imbalance in ferroptosis. In this review, we will provide an overview of lipid peroxidation, as well as key components involved in the ferroptotic cascade. The main mechanism that reduces ROS is the redox ability of glutathione (GSH). GSH, a tripeptide that includes glutamic acid, cysteine, and glycine, acts as an antioxidant and is the substrate of glutathione peroxidase 4 (GPX4), which is then converted into oxidized glutathione (GSSG). Increasing the expression of GSH can inhibit ferroptosis. We highlight the role of the x(c)(-) GSH-GPX4 pathway as the main pathway to regulate ferroptosis. The system x(c)(-), composed of subunit solute carrier family members (SLC7A11 and SLC3A2), mediates the exchange of cystine and glutamate across the plasma membrane to synthesize GSH. Accumulating evidence indicates that ferroptosis requires the autophagy machinery for its execution. Ferritinophagy is used to describe the removal of the major iron storage protein ferritin by the autophagy machinery. Nuclear receptor coactivator 4 (NCOA4) is a cytosolic autophagy receptor used to bind ferritin for subsequent degradation by ferritinophagy. During ferritinophagy, stored iron released becomes available for biosynthetic pathways. The dysfunctional ferroptotic response is implicated in a variety of pathological conditions. Ferroptosis inducers or inhibitors targeting redox- or iron metabolism-related proteins and signal transduction have been developed. The simultaneous detection of intracellular and extracellular markers may help diagnose and treat diseases related to ferroptotic damage.
format Online
Article
Text
id pubmed-9820499
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98204992023-01-07 Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis Rochette, Luc Dogon, Geoffrey Rigal, Eve Zeller, Marianne Cottin, Yves Vergely, Catherine Int J Mol Sci Review Regulated cell death (RCD) has a significant impact on development, tissue homeostasis, and the occurrence of various diseases. Among different forms of RCD, ferroptosis is considered as a type of reactive oxygen species (ROS)-dependent regulated necrosis. ROS can react with polyunsaturated fatty acids (PUFAs) of the lipid (L) membrane via the formation of a lipid radical L• and induce lipid peroxidation to form L-ROS. Ferroptosis is triggered by an imbalance between lipid hydroperoxide (LOOH) detoxification and iron-dependent L-ROS accumulation. Intracellular iron accumulation and lipid peroxidation are two central biochemical events leading to ferroptosis. Organelles, including mitochondria and lysosomes are involved in the regulation of iron metabolism and redox imbalance in ferroptosis. In this review, we will provide an overview of lipid peroxidation, as well as key components involved in the ferroptotic cascade. The main mechanism that reduces ROS is the redox ability of glutathione (GSH). GSH, a tripeptide that includes glutamic acid, cysteine, and glycine, acts as an antioxidant and is the substrate of glutathione peroxidase 4 (GPX4), which is then converted into oxidized glutathione (GSSG). Increasing the expression of GSH can inhibit ferroptosis. We highlight the role of the x(c)(-) GSH-GPX4 pathway as the main pathway to regulate ferroptosis. The system x(c)(-), composed of subunit solute carrier family members (SLC7A11 and SLC3A2), mediates the exchange of cystine and glutamate across the plasma membrane to synthesize GSH. Accumulating evidence indicates that ferroptosis requires the autophagy machinery for its execution. Ferritinophagy is used to describe the removal of the major iron storage protein ferritin by the autophagy machinery. Nuclear receptor coactivator 4 (NCOA4) is a cytosolic autophagy receptor used to bind ferritin for subsequent degradation by ferritinophagy. During ferritinophagy, stored iron released becomes available for biosynthetic pathways. The dysfunctional ferroptotic response is implicated in a variety of pathological conditions. Ferroptosis inducers or inhibitors targeting redox- or iron metabolism-related proteins and signal transduction have been developed. The simultaneous detection of intracellular and extracellular markers may help diagnose and treat diseases related to ferroptotic damage. MDPI 2022-12-27 /pmc/articles/PMC9820499/ /pubmed/36613888 http://dx.doi.org/10.3390/ijms24010449 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Rochette, Luc
Dogon, Geoffrey
Rigal, Eve
Zeller, Marianne
Cottin, Yves
Vergely, Catherine
Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
title Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
title_full Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
title_fullStr Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
title_full_unstemmed Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
title_short Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis
title_sort lipid peroxidation and iron metabolism: two corner stones in the homeostasis control of ferroptosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820499/
https://www.ncbi.nlm.nih.gov/pubmed/36613888
http://dx.doi.org/10.3390/ijms24010449
work_keys_str_mv AT rochetteluc lipidperoxidationandironmetabolismtwocornerstonesinthehomeostasiscontrolofferroptosis
AT dogongeoffrey lipidperoxidationandironmetabolismtwocornerstonesinthehomeostasiscontrolofferroptosis
AT rigaleve lipidperoxidationandironmetabolismtwocornerstonesinthehomeostasiscontrolofferroptosis
AT zellermarianne lipidperoxidationandironmetabolismtwocornerstonesinthehomeostasiscontrolofferroptosis
AT cottinyves lipidperoxidationandironmetabolismtwocornerstonesinthehomeostasiscontrolofferroptosis
AT vergelycatherine lipidperoxidationandironmetabolismtwocornerstonesinthehomeostasiscontrolofferroptosis