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Review
. 2022 Feb 24;13(2):182.
doi: 10.1038/s41419-022-04628-9.

Targeting ferroptosis in acute kidney injury

Lihua Ni  1 , Cheng Yuan  2 , Xiaoyan Wu  3
Affiliations
Review

Targeting ferroptosis in acute kidney injury

Lihua Ni et al. Cell Death Dis. .

Abstract

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As a form of programmed cell death (PCD), ferroptosis could be considered as a process of iron accumulation and enhanced lipid peroxidation. Recently, the fundamental roles of ferroptosis in AKI have attracted much attention. The network mechanism of ferroptosis in AKI and its roles in the AKI to chronic kidney disease (CKD) transition is complicated and multifactorial. Strategies targeting ferroptosis show great potential. Here, we review the research progress on ferroptosis and its participation in AKI. We hope that this work will provide clues for further studies of ferroptosis in AKI.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Schematic representation of the main types of cell death.
Cell death can be classified into programmed cell death (PCD, such as ferroptosis, apoptosis, and autophagy) and accidental cell death (such as necrosis).
Fig. 2
Fig. 2. Regulatory mechanism of ferroptosis.
General mechanism of ferroptosis associated with System Xc−, GPX4, iron homeostasis, ROS, and lipid peroxidation.
Fig. 3
Fig. 3. The interplay between mitochondria, lysosomes, the ER, and the Golgi in ferroptosis.
Mitochondria and lysosomes together participate in iron metabolism, which induces ferroptosis. In addition, mitochondrial ROS can be taken up by lysosomes, ultimately leading to ferroptosis. ER stress can induce the function of the Golgi, which regulates ferroptosis.
Fig. 4
Fig. 4. The roles of ferroptosis in AKI and the AKI to CKD transition.
Ferroptosis induces necroptosis, autophagy, and inflammatory responses, which lead to the progression of AKI. In some cases, ferroptosis and necroptosis act in a synergic or sequential fashion. In addition, targeting ferroptosis can alleviate tubular injury, mitochondrial function, and the inflammatory response, which further contribute to the AKI to CKD transition. However, direct evidence of ferroptosis in the AKI to CKD transition is lacking.
Fig. 5
Fig. 5. Ferroptosis-targeted treatment in AKI.
In rodent models of AKI, pharmacological inhibitors of ferroptosis can be employed to alleviate ferroptosis in AKI.
See this image and copyright information in PMC

References

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