An archaeal NADH oxidase causes damage to both proteins and nucleic acids under oxidative stress

Mol Cells. 2010 Apr;29(4):363-71. doi: 10.1007/s10059-010-0045-8. Epub 2010 Mar 4.


NADH oxidases (NOXs) catalyze the two-electron reduction of oxygen to H2O2 or four-electron reduction of oxygen to H2O. In this report, we show that an NADH oxidase from Thermococcus profundus (NOXtp) displays two forms: a native dimeric protein under physiological conditions and an oxidized hexameric form under oxidative stress. Native NOXtp displays high NADH oxidase activity, and oxidized NOXtp can accelerate the aggregation of partially unfolded proteins. The aggregates formed by NOXtp have characteristics similar to beta-amyloid and Lewy bodies in neurodegenerative diseases, including an increase of beta-sheet content. Oxidized NOXtp can also bind nucleic acids and cause their degradation by oxidizing NADH to produce H2O2. Furthermore, Escherichia coli cells expressing NOXtp are less viable than cells not expressing NOXtp after treatment with H2O2. As NOXtp shares similar features with eukaryotic cell death isozymes and life may have originated from hyperthermophiles, we suggest that NOXtp may be an ancestor of cell death proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaeal Proteins / chemistry
  • Archaeal Proteins / metabolism*
  • Archaeal Proteins / ultrastructure
  • Blotting, Western
  • DNA Damage
  • DNA, Archaeal / genetics
  • DNA, Archaeal / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Microbial Viability / genetics
  • Microscopy, Electron
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism*
  • Multienzyme Complexes / ultrastructure
  • NADH, NADPH Oxidoreductases / chemistry
  • NADH, NADPH Oxidoreductases / metabolism*
  • NADH, NADPH Oxidoreductases / ultrastructure
  • Oxidation-Reduction
  • Oxidative Stress*
  • Protein Conformation / drug effects
  • Protein Multimerization
  • RNA, Archaeal / genetics
  • RNA, Archaeal / metabolism
  • Temperature
  • Thermococcus / enzymology*


  • Archaeal Proteins
  • DNA, Archaeal
  • Multienzyme Complexes
  • RNA, Archaeal
  • Hydrogen Peroxide
  • NADH oxidase
  • NADH, NADPH Oxidoreductases