Open AccessNovel Roles of Necroptosis Mediator Receptor-Interacting Protein Kinase 3 in Kidney Injury
Author(s) -
Rie Uni,
Mary E. Choi
Publication year - 2021
Publication title -
the nephron journals/nephron journals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.951
H-Index - 72
eISSN - 2235-3186
pISSN - 1660-8151
DOI - 10.1159/000517732
Subject(s) - necroptosis , acute kidney injury , microbiology and biotechnology , kidney , medicine , programmed cell death , ripk1 , cancer research , mediator , kinase , signal transduction , biology , apoptosis , biochemistry
Necroptosis is a programmed cell death that is characterized by regulated necrosis resulting in plasma membrane rupture and subsequent release of damage-associated molecular patterns (DAMPs). Receptor-interacting protein kinase 3 (RIPK3) is a key mediator of this pathway. Accumulating evidence supports a critical role of RIPK3 and the necroptosis pathway in various human diseases. In this review, we discuss recent investigations that have uncovered pathogenic roles of RIPK3 in both acute kidney injury (AKI) and kidney fibrosis. RIPK3 promotes kidney tubular injury via a mechanism involving mitochondrial dysfunction. Additionally, extracellular mitochondrial DNA, which is one of the necroptotic DAMPs, released from damaged mitochondria correlates with kidney tubular injury and represents a potential novel biomarker. RIPK3 also induces kidney fibrogenesis through AKT-dependent activation of the metabolic enzyme ATP citrate lyase. Thus, the RIPK3-mediated necroptosis pathway may serve as a promising new therapeutic target in AKI and kidney fibrosis.