Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis

Konstantin G Lyamzaev; Alisa A Panteleeva; Ruben A Simonyan; Armine V Avetisyan; Boris V Chernyak

doi:10.3390/cells12040611

Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis

Cells. 2023 Feb 13;12(4):611. doi: 10.3390/cells12040611.

Authors

Konstantin G Lyamzaev^{1

2}, Alisa A Panteleeva¹, Ruben A Simonyan¹, Armine V Avetisyan¹, Boris V Chernyak¹

Affiliations

¹ Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
² The "Russian Clinical Research Center for Gerontology" of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, 129226 Moscow, Russia.

Abstract

Ferroptosis induced by erastin (an inhibitor of cystine transport) and butionine sulfoximine (an inhibitor of glutathione biosynthesis) was prevented by the mitochondria-targeted antioxidants SkQ1 and MitoTEMPO. These effects correlate with the prevention of mitochondrial lipid peroxidation, which precedes cell death. Methylene blue, a redox agent that inhibits the production of reactive oxygen species (ROS) in complex I of the mitochondrial electron transport chain, also inhibits ferroptosis and mitochondrial lipid peroxidation. Activation of ROS production in complex I with rotenone in the presence of ferrous iron stimulates lipid peroxidation in isolated mitochondria, while ROS produced by complex III are ineffective. SkQ1 and methylene blue inhibit lipid peroxidation. We suggest that ROS formed in complex I promote mitochondrial lipid peroxidation and ferroptosis.

Keywords: complex I; ferroptosis; mitochondria; mitochondria targeted antioxidants; mtROS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ferroptosis*
Lipid Peroxidation
Methylene Blue / metabolism
Mitochondria / metabolism
Reactive Oxygen Species / metabolism

Substances

Reactive Oxygen Species
Methylene Blue

Grants and funding

This research received no external funding.