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Exogenous Iron Induces Mitochondrial Lipid Peroxidation, Lipofuscin Accumulation, and Ferroptosis in H9c2 Cardiomyocytes

Authors :
Konstantin G. Lyamzaev
He Huan
Alisa A. Panteleeva
Ruben A. Simonyan
Armine V. Avetisyan
Boris V. Chernyak
Source :
Biomolecules, Vol 14, Iss 6, p 730 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation during ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate at submillimolar doses induces production of reactive oxygen species (ROS) and lipid peroxidation in mitochondria that precede ferroptosis in H9c2 cardiomyocytes. The mitochondria-targeted antioxidant SkQ1 and the redox mediator methylene blue, which inhibits the production of ROS in complex I of the mitochondrial electron transport chain, prevent both mitochondrial lipid peroxidation and ferroptosis. SkQ1 and methylene blue also prevented accumulation of lipofuscin observed after 24 h incubation of cardiomyocytes with ferric ammonium citrate. Using isolated cardiac mitochondria as an in vitro ferroptosis model, it was shown that rotenone (complex I inhibitor) in the presence of ferrous iron stimulates lipid peroxidation and lipofuscin accumulation. Our data indicate that ROS generated in complex I stimulate mitochondrial lipid peroxidation, lipofuscin accumulation, and ferroptosis induced by exogenous iron.

Details

Language :
English
ISSN :
2218273X
Volume :
14
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.32d22f44b64d288a76ed595cc66194
Document Type :
article
Full Text :
https://doi.org/10.3390/biom14060730