Journal of Biological Chemistry
Volume 279, Issue 18, 30 April 2004, Pages 18188-18194
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Membrane Transport, Structure, Function, and Biogenesis
Biogenesis of the Protein Import Channel Tom40 of the Mitochondrial Outer Membrane: INTERMEMBRANE SPACE COMPONENTS ARE INVOLVED IN AN EARLY STAGE OF THE ASSEMBLY PATHWAY*

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Tom40 forms the central channel of the preprotein translocase of the mitochondrial outer membrane (TOM complex). The precursor of Tom40 is encoded in the nucleus, synthesized in the cytosol, and imported into mitochondria via a multi-step assembly pathway that involves the mature TOM complex and the sorting and assembly machinery of the outer membrane (SAM complex). We report that opening of the mitochondrial intermembrane space by swelling blocks the assembly pathway of the β-barrel protein Tom40. Mitochondria with defects in small Tim proteins of the intermembrane space are impaired in the Tom40 assembly pathway. Swelling as well as defects in the small Tim proteins inhibit an early stage of the Tom40 import pathway that is needed for formation of a Tom40-SAM intermediate. We propose that the biogenesis pathway of β-barrel proteins of the outer mitochondrial membrane not only requires TOM and SAM components, but also involves components of the intermembrane space.

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This work was supported by the Deutsche Forschungsgemeinschaft, the Sonderforschungsbereich 388, a Max Planck Research Award, the Alexander von Humboldt Foundation, the Bundesministerium für Bildung und Forschung, and the Fonds der Chemischen Industrie. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.