Biogenesis of Tom40, Core Component of the TOM Complex of Mitochondria

doi:10.1083/jcb.146.2.321

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J. Cell Biol., Volume 146, Number 2, July 26, 1999 321-332
Copyright © 1999 by The Rockefeller University Press.

Biogenesis of Tom40, Core Component of the TOM Complex of Mitochondria

Doron Rapaport^a and Walter Neupert^a
^a Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie der Universität München, 80336 München, Germany

Correspondence to: Walter Neupert, Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie der Universität München, Goethestrasse 33, 80336 München, Germany., neupert{at}bio.med.uni-muenchen.de (E-mail), 49-89-5996 312 (phone), 49-89-5996 270 (fax)

Tom40 is an essential component of the preprotein translocaseof the mitochondrial outer membrane (TOM complex) in which itconstitutes the core element of the protein conducting pore.We have investigated the biogenesis of Tom40. Tom40 is insertedinto the outer membrane by the TOM complex. Initially, Tom40is bound as a monomer at the mitochondrial surface. The importreceptor Tom20 is involved in this initial step; it stimulatesboth binding and efficient insertion of the Tom40 precursor.This step is followed by the formation of a further intermediateat which the Tom40 precursor is partially inserted into theouter membrane. Finally, Tom40 is integrated into preexistingTOM complexes. Efficient import appears to require the Tom40precursor to be in a partially folded conformation. Neitherthe NH₂ nor the COOH termini are necessary to target Tom40 tothe outer membrane. However, the NH₂-terminal segment is requiredfor Tom40 to become assembled into the TOM complex. A modelfor the biogenesis of Tom40 is presented.

Key Words: mitochondrial protein import, TOM complex, Tom40, protein insertion,unfolding

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