1. Adolf-Butenandt-Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5, D-81377 München, Germany
2. Max-Planck-Institut für Biochemie, Abteilung für Molekulare Strukturbiologie, Am Klopferspitz 18a, D-82152 Martinsried, Germany
3. These authors contributed equally to this work

Correspondence to: Walter Neupert¹ Email: Neupert@bio.med.uni-muenchen.de

Abstract

The outer membranes of mitochondria and chloroplasts are distinguished by the presence of -barrel membrane proteins^{1, 2}. The outer membrane of Gram-negative bacteria also harbours -barrel proteins³. In mitochondria these proteins fulfil a variety of functions such as transport of small molecules (porin/VDAC), translocation of proteins (Tom40) and regulation of mitochondrial morphology (Mdm10)^{4, 5, 6, 7}. These proteins are encoded by the nucleus, synthesized in the cytosol, targeted to mitochondria as chaperone-bound species, recognized by the translocase of the outer membrane, and then inserted into the outer membrane where they assemble into functional oligomers^{8, 9, 10, 11}. Whereas some knowledge has been accumulated on the pathways of insertion of proteins that span cellular membranes with -helical segments, very little is known about how -barrel proteins are integrated into lipid bilayers and assembled into oligomeric structures¹². Here we describe a protein complex that is essential for the topogenesis of mitochondrial outer membrane -barrel proteins (TOB). We present evidence that important elements of the topogenesis of -barrel membrane proteins have been conserved during the evolution of mitochondria from endosymbiotic bacterial ancestors¹³.