Exogenous Monounsaturated Fatty Acids Promote a Ferroptosis-Resistant Cell State.

Animals Arachidonic Acid / chemistry Cell Line Cell Membrane / chemistry Coenzyme A Ligases / metabolism Fatty Acids, Monounsaturated / chemistry Ferroptosis / drug effects Lipid Droplets / chemistry Lipids / chemistry Mice Oxidation-Reduction Phospholipid Hydroperoxide Glutathione Peroxidase / genetics Reactive Oxygen Species / chemistry
GPX4 MUFAs cell death ferroptosis iron lipid ROS lipid droplet lipotoxicity oleate

Journal

Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030

Informations de publication

Date de publication:
21 03 2019
Historique:
received: 17 04 2018
revised: 18 09 2018
accepted: 27 11 2018
pubmed: 29 1 2019
medline: 31 12 2019
entrez: 29 1 2019
Statut: ppublish

Résumé

The initiation and execution of cell death can be regulated by various lipids. How the levels of environmental (exogenous) lipids impact cell death sensitivity is not well understood. We find that exogenous monounsaturated fatty acids (MUFAs) potently inhibit the non-apoptotic, iron-dependent, oxidative cell death process of ferroptosis. This protective effect is associated with the suppression of lipid reactive oxygen species (ROS) accumulation at the plasma membrane and decreased levels of phospholipids containing oxidizable polyunsaturated fatty acids. Treatment with exogenous MUFAs reduces the sensitivity of plasma membrane lipids to oxidation over several hours. This effect requires MUFA activation by acyl-coenzyme A synthetase long-chain family member 3 (ACSL3) and is independent of lipid droplet formation. Exogenous MUFAs also protect cells from apoptotic lipotoxicity caused by the accumulation of saturated fatty acids, but in an ACSL3-independent manner. Our work demonstrates that ACSL3-dependent MUFA activation promotes a ferroptosis-resistant cell state.

Identifiants

DOI: 10.1016/j.chembiol.2018.11.016 PMID: 30686757 PMC: PMC6430697
pubmed: 30686757
pii: S2451-9456(18)30438-0
doi: 10.1016/j.chembiol.2018.11.016
pmc: PMC6430697
mid: NIHMS1516534
pii:
doi:

Substances chimiques

Fatty Acids, Monounsaturated 0
Lipids 0
Reactive Oxygen Species 0
Arachidonic Acid 27YG812J1I
Phospholipid Hydroperoxide Glutathione Peroxidase EC 1.11.1.12
glutathione peroxidase 4, mouse EC 1.11.1.9
Acsl3 protein, mouse EC 6.1.2.3
Coenzyme A Ligases EC 6.2.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

420-432.e9

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM122923
Pays : United States
Organisme : NCI NIH HHS
ID : F99 CA234650
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172667
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007276
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK098722
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA234650
Pays : United States
Organisme : NIEHS NIH HHS
ID : R35 ES028365
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM112948
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2018 Elsevier Ltd. All rights reserved.

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Auteurs

Leslie Magtanong (L)

Department of Biology, Stanford University, Stanford, CA 94305, USA.

Pin-Joe Ko (PJ)

Department of Biology, Stanford University, Stanford, CA 94305, USA.

Milton To (M)

Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.

Jennifer Yinuo Cao (JY)

Department of Biology, Stanford University, Stanford, CA 94305, USA.

Giovanni C Forcina (GC)

Department of Biology, Stanford University, Stanford, CA 94305, USA.

Amy Tarangelo (A)

Department of Biology, Stanford University, Stanford, CA 94305, USA.

Carl C Ward (CC)

Departments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

Kevin Cho (K)

Departments of Chemistry and Medicine, Washington University, St. Louis, MO 63130, USA.

Gary J Patti (GJ)

Departments of Chemistry and Medicine, Washington University, St. Louis, MO 63130, USA.

Daniel K Nomura (DK)

Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Departments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

James A Olzmann (JA)

Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.

Scott J Dixon (SJ)

Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: sjdixon@stanford.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Lipides › Acides gras › Acides gras insaturés › Acides gras indispensables › Acides arachidoniques › Acide arachidonique › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Carbon-sulfur ligases › Coenzyme A ligases › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Lipides › Acides gras › Acides gras insaturés › Acides gras monoinsaturés › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Ferroptose › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Gouttelettes lipidiques › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Lipides › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Métabolisme › Métabolisme énergétique › Oxydoréduction › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Sélénoprotéines › Glutathione peroxidase › Phospholipid hydroperoxide glutathione peroxidase › Exogenous Monounsaturated Fatty Acids Promote...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Exogenous Monounsaturated Fatty Acids Promote...