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

Lili Tian; Jianming Chen; Mingliang Chen; Chloe Gui; Chuan-Qi Zhong; Lixin Hong; Changchuan Xie; Xiurong Wu; Lirong Yang; Vakil Ahmad; Jiahuai Han

doi:10.1074/jbc.M114.589093

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.

Authors

Affiliations

¹ State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
² Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration (SOA), Xiamen, Fujian 361005, China, and. Electronic address: [email protected].
³ Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration (SOA), Xiamen, Fujian 361005, China, and.
⁴ Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

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