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Phosphorylation of flotillin‐1 by mitochondrial c‐Src is required to prevent the production of reactive oxygen species
Author(s) -
Ogura Masato,
Yamaki Junko,
Homma Miwako K.,
Homma Yoshimi
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.06.044
Subject(s) - phosphorylation , proto oncogene tyrosine protein kinase src , reactive oxygen species , microbiology and biotechnology , chemistry , mitochondrial ros , mitochondrion , kinase , biology
We have shown that mitochondrial c‐Src regulates reactive oxygen species (ROS) production by phosphorylating the succinate dehydrogenase A of respiratory complex II (CxII). To elucidate the molecular mechanisms underlying ROS production regulated by c‐Src in the CxII, we investigated the CxII protein complex derived from cells treated with Src family kinase inhibitor PP2. We identified flotillin‐1 as a c‐Src target that prevents ROS production from CxII. Phosphorylation‐site analysis suggests Tyr56 and Tyr149 on flotillin‐1 as sites for phosphorylation by c‐Src. A comparison of cells expressing flotillin‐1 and its phosphorylation defective mutants confirms the requirement for flotillin‐1 phosphorylation for its interaction with CxII and subsequent reduction in ROS production. Our findings suggest a critical role of flotillin‐1 in ROS production mediated by c‐Src.