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Seibt, T. ; Wahida, A. ; Hoeft, K.* ; Kemmner, S.* ; Linkermann, A.* ; Mishima, E. ; Conrad, M.

The biology of ferroptosis in kidney disease.

Nephrol. Dial. Transplant. 39, 1754-1761 (2024)
Postprint DOI PMC
Open Access Green
Free by publisher: Publ. Version/Full Text online available 07/2025
Ferroptosis is a regulated cell death modality triggered by iron-dependent lipid peroxidation. Ferroptosis plays a causal role in the pathophysiology of various diseases, making it a promising therapeutic target. Unlike all other cell death modalities dependent on distinct signaling cues, ferroptosis occurs when cellular antioxidative defense mechanisms fail to suppress the oxidative destruction of cellular membranes, eventually leading to cell membrane rupture. Physiologically, only two such surveillance systems are known to efficiently prevent the lipid peroxidation chain reaction by reducing (phospho)lipid hydroperoxides to their corresponding alcohols or by reducing radicals in phospholipid bilayers, thus maintaining the integrity of lipid membranes. Mechanistically, these two systems are linked to the reducing capacity of glutathione peroxidase 4 (GPX4) by consuming glutathione (GSH) on the one and ferroptosis suppressor protein 1 (FSP1, formerly AIFM2) on the other hand. Notably, the importance of ferroptosis suppression in physiological contexts has been linked to a particular vulnerability of renal tissue. In fact, early work has shown that mice genetically lacking Gpx4 rapidly succumb to acute renal failure with pathohistological features of acute tubular necrosis. Promising research attempting to implicate ferroptosis in various renal disease entities, particularly those with proximal tubular involvement, has generated a wealth of knowledge with widespread potential for clinical translation. Here, we provide a brief overview of the involvement of ferroptosis in nephrology. Our goal is to introduce this expanding field for clinically versed nephrologists in the hope of spurring future efforts to prevent ferroptosis in the pathophysiological processes of the kidney.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Gpx4 ; Acute Kidney Injury ; Ferroptosis ; Iron Metabolism ; Lipid Peroxidation
ISSN (print) / ISBN 0931-0509
e-ISSN 1460-2385
Journal Nephrology Dialysis Transplantation
Quellenangaben Volume: 39, Issue: 11, Pages: 1754-1761 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)