AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins

doi:10.1083/jcb.200305051

Published 13 October 2003. doi:10.1083/jcb.200305051

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Article

AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins

Masato Yano, Kazutoyo Terada and Masataka Mori

Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan

Address correspondence to Masato Yano, Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan. Tel.: 81-96-373-5140. Fax: 81-96-373-5145. email: myano{at}gpo.kumamoto-u.ac.jp; or Masataka Mori, Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan. Tel.: 81-96-373-5140. Fax: 81-96-373-5145. email: masa{at}gpo.kumamoto-u.ac.jp

Most mitochondrial preproteins are maintained in a loosely foldedimport-competent conformation by cytosolic chaperones, and areimported into mitochondria by translocator complexes containinga preprotein receptor, termed translocase of the outer membraneof mitochondria (Tom) 20. Using two-hybrid screening, we identifiedarylhydrocarbon receptor–interacting protein (AIP), anFK506-binding protein homologue, interacting with Tom20. Theextreme COOH-terminal acidic segment of Tom20 was required forinteraction with tetratricopeptide repeats of AIP. An in vitroimport assay indicated that AIP prevents preornithine transcarbamylasefrom the loss of import competency. In cultured cells, overexpressionof AIP enhanced preornithine transcarbamylase import, and depletionof AIP by RNA interference impaired the import. An in vitrobinding assay revealed that AIP specifically binds to mitochondrialpreproteins. Formation of a ternary complex of Tom20, AIP, andpreprotein was observed. Hsc70 was also found to bind to AIP.An aggregation suppression assay indicated that AIP has a chaperone-likeactivity to prevent substrate proteins from aggregation. Theseresults suggest that AIP functions as a cytosolic factor thatmediates preprotein import into mitochondria.

Key Words: chaperone; import competency; protein targeting; mitochondria; Tom20

Abbreviations used in this paper: AhR, arylhydrocarbon receptor;AIP, arylhydrocarbon receptor–interacting protein; ECHS1,enoyl-coenzyme A hydratase 1 precursor; FKBP52, 52-kD FK506-bindingprotein; hTom20, human Tom20; MBP, maltose-binding protein;NDUFB10, NADH:ubiquinone oxidoreductase 1ß subcomplex10; OTC, ornithine transcarbamylase; pOTC, preornithine transcarbamylase;PPIase, peptidyl-prolyl cis/trans isomerase; siRNA, small interferingRNA; Tom, translocase of the outer membrane of mitochondria;TPR, tetratricopeptide repeat.

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