Lifespan extension by peroxidase and dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in C. elegans

J Cell Sci. 2017 Aug 1;130(15):2631-2643. doi: 10.1242/jcs.202119. Epub 2017 Jul 4.


Reactive oxygen species (ROS), originally characterized based on their harmful effects on cells or organisms, are now recognized as important signal molecules regulating various biological processes. In particular, low levels of ROS released from mitochondria extend lifespan. Here, we identified a novel mechanism of generating appropriate levels of ROS at the plasma membrane through a peroxidase and dual oxidase (DUOX) system, which could extend lifespan in Caenorhabditis elegans A redox co-factor, pyrroloquinoline quinone (PQQ), activates the C. elegans DUOX protein BLI-3 to produce the ROS H2O2 at the plasma membrane, which is subsequently degraded by peroxidase (MLT-7), eventually ensuring adequate levels of ROS. These ROS signals are transduced mainly by the oxidative stress transcriptional factors SKN-1 (Nrf2 or NFE2L2 in mammals) and JUN-1, and partially by DAF-16 (a FOXO protein homolog). Cell biology experiments demonstrated a similarity between the mechanisms of PQQ-induced activation of human DUOX1 and DUOX2 and that of C. elegans BLI-3, suggesting that DUOXs are potential targets of intervention for lifespan extension. We propose that low levels of ROS, fine-tuned by the peroxidase and dual oxidase system at the plasma membrane, act as second messengers to extend lifespan by the effect of hormesis.

Keywords: C. elegans; Dual oxidase; Lifespan; Peroxidase; Pyrroloquinoline quinone; Reactive oxygen species.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Dual Oxidases / genetics
  • Dual Oxidases / metabolism*
  • Longevity / physiology*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • PQQ Cofactor / genetics
  • PQQ Cofactor / metabolism*
  • Peroxidase / genetics
  • Peroxidase / metabolism*
  • Reactive Oxygen Species / metabolism*


  • Caenorhabditis elegans Proteins
  • Reactive Oxygen Species
  • PQQ Cofactor
  • Bli-3 protein, C elegans
  • Oxidoreductases
  • Dual Oxidases
  • Peroxidase