Nlrx1 regulates neuronal cell death

Mol Brain. 2014 Dec 24:7:90. doi: 10.1186/s13041-014-0090-x.

Abstract

Background: Regulation of cell death during neurodegeneration is one of the key factors that play a role in the speed at which a disease progresses. Out of several cellular pathways responsible for this progression, necrosis and apoptosis are situated on the opposite spectrum of cell death regulation. Necrosis produces an environment that promotes inflammation and cytotoxicity and apoptosis is a highly organized process that maintains tissue homeostasis. A recently discovered protein, Nlrx1, regulates inflammatory and cell death responses during infection.

Findings: Using transfections of N2A cell line, we demonstrate that Nlrx1 redirects cells away from necrosis and towards an apoptotic pathway following rotenone treatments. In addition, Nlrx1 promotes DRP1 phosphorylation and increases mitochondrial fission.

Conclusion: Our results suggest a novel molecular pathway for regulating mitochondrial dynamics and neuronal death. Nlrx1 may play an important role in neurodegenerative diseases, where necrosis is a prominent factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Dynamins / metabolism
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondrial Dynamics / drug effects
  • Mitochondrial Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Neuroprotective Agents / pharmacology
  • Quinazolinones / pharmacology
  • Rotenone / pharmacology

Substances

  • 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone
  • Mitochondrial Proteins
  • NLRX1 protein, mouse
  • Neuroprotective Agents
  • Quinazolinones
  • Rotenone
  • Dnm1l protein, mouse
  • Dynamins