The Necrosome in Acute Kidney Injury

Semin Nephrol. 2016 May;36(3):199-207. doi: 10.1016/j.semnephrol.2016.03.007.

Abstract

Cell death and inflammation in the proximal tubules are the hallmarks of acute kidney injury (AKI), but the underlying mechanism has not been fully elucidated. Recent evidence has shown that necroptosis, a type of programmed necrosis, plays an important role in AKI. The necrosis-inducing signaling complex is called the necrosome, which contains receptor-interacting protein 1, receptor-interacting protein 3, and mixed lineage kinase domain-like protein. Studies have found that inhibition of the core components of the necroptotic pathway by gene knockout, RNA interference, or a chemical inhibitor diminished proximal tubule damage, showing that necroptosis is a major contributor to AKI. This review focuses on the functional roles of the necrosome in regulating renal tubular cell necroptosis, and the physiological and pathologic roles of necrosome in AKI.

Keywords: Necrosome; acute kidney injury; necroptosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / metabolism*
  • Apoptosis*
  • Humans
  • Kidney Tubules, Proximal / pathology
  • Necrosis*
  • Protein Kinases / metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*

Substances

  • MLKL protein, human
  • Protein Kinases
  • RIPK1 protein, human
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases