title: Regulated cell death in AKI.
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.
authors.affiliation: Clinic for Nephrology and Hypertension, Christian-Albrechts-University, Kiel, Germany; zdong@gru.edu andreas.linkermann@uksh.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Linkermann
authors.affiliation: Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and.
authors.forename: Guochun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Cellular Biology and Anatomy, Charlie Norwood Veterans Affairs Medical Center and Medical College of Georgia at Georgia Regents University, Augusta, Georgia.
authors.forename: Guie
authors.initials: G
authors.lastname: Dong
authors.affiliation: Clinic for Nephrology and Hypertension, Christian-Albrechts-University, Kiel, Germany;
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kunzendorf
authors.affiliation: Clinic for Nephrology and Hypertension, Christian-Albrechts-University, Kiel, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Krautwald
authors.affiliation: Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and Department of Cellular Biology and Anatomy, Charlie Norwood Veterans Affairs Medical Center and Medical College of Georgia at Georgia Regents University, Augusta, Georgia zdong@gru.edu andreas.linkermann@uksh.de.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002463:Cell Membrane Permeability; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D020287:In Situ Nick-End Labeling; D007501:Iron / Q000737:chemistry; D007668:Kidney / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D007501:Iron
keywords: acute renal failure; apoptosis; renal injury