Regulated cell death in AKI

Andreas Linkermann, Guochun Chen, Guie Dong, Ulrich Kunzendorf, Stefan Krautwald, Zheng Dong

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166 Scopus citations

Abstract

AKI is pathologically characterized by sublethal and lethal damage of renal tubules. Under these conditions, renal tubular cell death may occur by regulated necrosis (RN) or apoptosis. In the last two decades, tubular apoptosis has been shown in preclinical models and some clinical samples from patients with AKI. Mechanistically, apoptotic cell death in AKI may result from well described extrinsic and intrinsic pathways as well as ER stress. Central converging nodes of these pathways are mitochondria, which become fragmented and sensitized to membrane permeabilization in response to cellular stress, resulting in the release of cell death-inducing factors. Whereas apoptosis is known to be regulated, tubular necrosis was thought to occur by accident until recent work unveiled several RN subroutines, most prominently receptor-interacting protein kinase-dependent necroptosis and RN induced by mitochondrial permeability transition. Additionally, other cell death pathways, like pyroptosis and ferroptosis, may also be of pathophysiologic relevance in AKI. Combination therapy targeting multiple cell-death pathways may, therefore, provide maximal therapeutic benefits.

Original languageEnglish (US)
Pages (from-to)2689-2701
Number of pages13
JournalJournal of the American Society of Nephrology
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

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ASJC Scopus subject areas

  • Nephrology

Cite this

Linkermann, A., Chen, G., Dong, G., Kunzendorf, U., Krautwald, S., & Dong, Z. (2014). Regulated cell death in AKI. Journal of the American Society of Nephrology, 25(12), 2689-2701. https://doi.org/10.1681/ASN.2014030262