title: Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein.
abstract: Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein.
authors.affiliation: Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea; School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea; Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Seong-Jeong
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Byung Cheon
authors.initials: BC
authors.lastname: Lee
authors.affiliation: Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Yim
authors.affiliation: Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.affiliation: Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea; Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Seung-Rock
authors.initials: SR
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004032:Diet; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008322:Mammals / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015203:Reproducibility of Results; D012643:Selenium / Q000378:metabolism; D051140:Selenoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D051140:Selenoproteins; D006861:Hydrogen Peroxide; D012643:Selenium
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