Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism

Cell Mol Life Sci. 2016 Sep;73(17):3221-47. doi: 10.1007/s00018-016-2223-0. Epub 2016 Apr 21.


The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. The vertebrate Nrf2 belongs to Cap 'n' Collar (Cnc) bZIP family of transcription factors and shares a high homology with SKN-1 from Caenorhabditis elegans or CncC found in Drosophila melanogaster. The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. HO-1 and their products exert beneficial effects through the protection against oxidative injury, regulation of apoptosis, modulation of inflammation as well as contribution to angiogenesis. On the other hand, the disturbances in the proper HO-1 level are associated with the pathogenesis of some age-dependent disorders, including neurodegeneration, cancer or macular degeneration. This review summarizes our knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors.

Keywords: Heme oxygenase-1 (HO-1); Kelch-like ECH-associated protein 1 (Keap1); Nuclear factor erythroid 2-related factor 2 (Nrf2); Oxidative stress; Reactive oxygen species (ROS).

Publication types

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

MeSH terms

  • Animals
  • Evolution, Molecular*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Longevity
  • MicroRNAs / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Repressor Proteins / metabolism


  • MicroRNAs
  • NF-E2-Related Factor 2
  • Protein Isoforms
  • Repressor Proteins
  • Heme Oxygenase-1
  • Proteasome Endopeptidase Complex