Characterization of the signal that directs Bcl-xL, but not Bcl-2, to the mitochondrial outer membrane

doi:10.1083/jcb.200210084

Epitomics: The Rabbit Monoclonal Company

Published 6 January 2003. doi:10.1083/jcb.200210084

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Article

Characterization of the signal that directs Bcl-x_L, but not Bcl-2, to the mitochondrial outer membrane

Thomas Kaufmann¹^,2, Sarah Schlipf¹, Javier Sanz², Karin Neubert¹, Reuven Stein³ and Christoph Borner¹

¹ Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, D-79106 Freiburg, Germany
² Institute of Biochemistry, University of Fribourg, CH-1700 Fribourg, Switzerland
³ Department of Neurobiochemistry, Tel-Aviv University, Tel-Aviv, 69978, Israel

Address correspondence to C. Borner, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Zentrale Klinische Forschung, Breisacherstrasse 66, D-79106 Freiburg, Germany. Tel.: 49-761-270-6217. Fax: 49-761-270-6218. E-mail: borner{at}ukl.uni-freiburg.de

It is assumed that the survival factors Bcl-2 and Bcl-x_L aremainly functional on mitochondria and therefore must containmitochondrial targeting sequences. Here we show, however, thatonly Bcl-x_L is specifically targeted to the mitochondrial outermembrane (MOM) whereas Bcl-2 distributes on several intracellularmembranes. Mitochondrial targeting of Bcl-x_L requires the COOH-terminaltransmembrane (TM) domain flanked at both ends by at least twobasic amino acids. This sequence is a bona fide targeting signalfor the MOM as it confers specific mitochondrial localizationto soluble EGFP. The signal is present in numerous proteinsknown to be directed to the MOM. Bcl-2 lacks the signal andtherefore localizes to several intracellular membranes. TheCOOH-terminal region of Bcl-2 can be converted into a targetingsignal for the MOM by increasing the basicity surrounding itsTM. These data define a new targeting sequence for the MOM andpropose that Bcl-2 acts on several intracellular membranes whereasBcl-x_L specifically functions on the MOM.

Key Words: apoptosis; Bcl-2; Bcl-x_L; mitochondria; ER

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