title: Phosphorylation of flotillin-1 by mitochondrial c-Src is required to prevent the production of reactive oxygen species.
abstract: 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.
authors.affiliation: Department of Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Department of Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Yamaki
authors.affiliation: Department of Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Miwako K
authors.initials: MK
authors.lastname: Homma
authors.affiliation: Department of Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan. Electronic address: yoshihom@fmu.ac.jp.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D042963:Electron Transport Complex II / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C106354:flotillins; C478189:respiratory complex II; D014443:Tyrosine; D042963:Electron Transport Complex II; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: Mitochondria; Protein phosphorylation; Reactive oxygen species; Respiratory complex; Tyrosine kinase; c-Src