Circadian Oscillation of Sulfiredoxin in the Mitochondria

Mol Cell. 2015 Aug 20;59(4):651-63. doi: 10.1016/j.molcel.2015.06.031. Epub 2015 Jul 30.

Abstract

Hydrogen peroxide (H2O2) released from mitochondria regulates various cell signaling pathways. Given that H2O2-eliminating enzymes such as peroxiredoxin III (PrxIII) are abundant in mitochondria, however, it has remained unknown how such release can occur. Active PrxIII-SH undergoes reversible inactivation via hyperoxidation to PrxIII-SO2, which is then reduced by sulfiredoxin. We now show that the amounts of PrxIII-SO2 and sulfiredoxin undergo antiphasic circadian oscillation in the mitochondria of specific tissues of mice maintained under normal conditions. Cytosolic sulfiredoxin was found to be imported into the mitochondria via a mechanism that requires formation of a disulfide-linked complex with heat shock protein 90, which is promoted by H2O2 released from mitochondria. The imported sulfiredoxin is degraded by Lon in a manner dependent on PrxIII hyperoxidation state. The coordinated import and degradation of sulfiredoxin provide the basis for sulfiredoxin oscillation and consequent PrxIII-SO2 oscillation in mitochondria and likely result in an oscillatory H2O2 release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm*
  • HeLa Cells
  • Heat-Shock Proteins / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / enzymology*
  • Organ Specificity
  • Oxidation-Reduction
  • Oxidoreductases Acting on Sulfur Group Donors / metabolism*
  • Peroxiredoxin III / metabolism
  • Protease La / metabolism
  • Protein Transport
  • Proteolysis
  • Sulfur Dioxide / metabolism
  • Tacrolimus Binding Proteins / metabolism

Substances

  • Heat-Shock Proteins
  • Prdx3 protein, mouse
  • Sulfur Dioxide
  • Hydrogen Peroxide
  • Peroxiredoxin III
  • Oxidoreductases Acting on Sulfur Group Donors
  • sulfiredoxin protein, mouse
  • Protease La
  • Tacrolimus Binding Proteins