The p38 pathway regulates oxidative stress tolerance by phosphorylation of mitochondrial protein IscU

J Biol Chem. 2014 Nov 14;289(46):31856-31865. doi: 10.1074/jbc.M114.589093. Epub 2014 Sep 9.

Abstract

The p38 pathway is an evolutionarily conserved signaling pathway that responds to a variety of stresses. However, the underlying mechanisms are largely unknown. In the present study, we demonstrate that p38b is a major p38 MAPK involved in the regulation of oxidative stress tolerance in addition to p38a and p38c in Drosophila. We further show the importance of MK2 as a p38-activated downstream kinase in resistance to oxidative stresses. Furthermore, we identified the iron-sulfur cluster scaffold protein IscU as a new substrate of MK2 both in Drosophila cells and in mammalian cells. These results imply a new mechanistic connection between the p38 pathway and mitochondria iron-sulfur clusters.

Keywords: Iron-Sulfur Protein; Mitochondrial Aconitase; Oxidative Stress; p38; p38 MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitate Hydratase / metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Electron Transport Complex I / metabolism
  • Gene Expression Regulation, Enzymologic
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism*
  • MAP Kinase Signaling System*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Sequence Data
  • Oxidative Stress*
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sequence Homology, Amino Acid

Substances

  • Drosophila Proteins
  • ISCU protein, human
  • Intracellular Signaling Peptides and Proteins
  • Iron-Sulfur Proteins
  • IscU protein, Drosophila
  • Mitochondrial Proteins
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • Aconitate Hydratase
  • Electron Transport Complex I