エンドウ トシヤ   ENDO TOSHIYA
  遠藤 斗志也
   所属   京都産業大学  生命科学部 先端生命科学科
   職種   客員教授
言語種別 英語
発行・発表の年月 2014/02
形態種別 研究論文
査読 査読あり
標題 Intramolecular Disulfide Bond of Tim22 Protein Maintains Integrity of the TIM22 Complex in the Mitochondrial Inner Membrane*
執筆形態 その他
掲載誌名 JOURNAL OF BIOLOGICAL CHEMISTRY
出版社・発行元 AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
巻・号・頁 289(8),pp.4827-4838
著者・共著者 Hiroaki Okamoto,Akiko Miyagawa,Takuya Shiota,Yasushi Tamura,Toshiya Endo
概要 Background: Tim22 is a central component of the mitochondrial inner membrane protein insertion machinery TIM22 complex. Results: Lack of the disulfide bond of Tim22 destabilizes Tim22 and impairs substrate protein assembly. Conclusion: The disulfide bond of Tim22 has a role in stabilization of the TIM22 complex, which is important for the TIM22 protein assembly pathway. Significance: Tim40(Mia40)/Erv1-independent disulfide bond formation contributes to protein stability in mitochondria.
Mitochondrial proteins require protein machineries called translocators in the outer and inner membranes for import into and sorting to their destination submitochondrial compartments. Among them, the TIM22 complex mediates insertion of polytopic membrane proteins into the inner membrane, and Tim22 constitutes its central insertion channel. Here we report that the conserved Cys residues of Tim22 form an intramolecular disulfide bond. By comparison of Tim22 Cys Ser mutants with wild-type Tim22, we show that the disulfide bond of Tim22 stabilizes Tim22 especially at elevated temperature through interactions with Tim18, which are also important for the stability of the TIM22 complex. We also show that lack of the disulfide bond in Tim22 impairs the assembly of TIM22 pathway substrate proteins into the inner membrane especially when the TIM22 complex handles excess amounts of substrate proteins. Our findings provide a new insight into the mechanism of the maintenance of the structural and functional integrity of the TIM22 complex.
DOI 10.1074/jbc.M113.543264
ISSN 0021-9258/1083-351X
PMID 24385427