Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 46, Pages 31856-31865Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.589093
Keywords
Iron-Sulfur Protein; Mitochondrial Aconitase; Oxidative Stress; p38; p38 MAPK
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Funding
- National Science Foundation [31171366]
- Marine Public Welfare Project [201005022]
- China Ocean Mineral Resources RD Association [DY125-15-T-03]
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Background: The p38 pathway is an evolutionarily conserved signaling pathway that responds to a variety of stresses. Results: dIscU can be phosphorylated by dMK2, thereby impacting mitochondrial respiratory complex I activity. Conclusion: Iron-sulfur cluster protein IscU phosphorylation by MK2 downstream of p38 signaling may regulate oxidative stress tolerance. Significance: IscU is a novel substrate of MK2, mechanistically connecting the p38 pathway and mitochondria iron-sulfur clusters for the first time. 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.
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