期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 8, 页码 4827-4838出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.543264
关键词
Disulfide; Membrane Proteins; Mitochondria; Protein Translocation; Yeast; Tim22
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- grant for CREST from the Japan Science and Technology Agency (JST)
- Grants-in-Aid for Scientific Research [22227003] Funding Source: KAKEN
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.
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