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

被引:283
作者
Kaufmann, T
Schlipf, S
Sanz, J
Neubert, K
Stein, R
Borner, C
机构
[1] Univ Freiburg, Inst Mol Med & Cell Res, D-79106 Freiburg, Germany
[2] Univ Fribourg, Inst Biochem, CH-1700 Fribourg, Switzerland
[3] Tel Aviv Univ, Dept Neurobiochem, IL-69978 Tel Aviv, Israel
关键词
apoptosis; Bcl-2; Bcl-x(L); mitochondria; ER;
D O I
10.1083/jcb.200210084
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
It is assumed that the survival factors Bcl-2 and Bcl-x(L) are mainly functional on mitochondria and therefore must contain mitochondrial targeting sequences. Here we show, however, that only Bcl-x(L) is specifically targeted to the mitochondrial outer membrane (MOM) whereas Bcl-2 distributes on several intracellular membranes. Mitochondrial targeting of Bcl-x(L) requires the COOH-terminal transmembrane (TM) domain flanked at both ends by at least two basic amino acids, This sequence is a bona fide targeting signal for the MOM as it confers specific mitochondrial localization to soluble EGFP. The signal is present in numerous proteins known to be directed to the MOM. Bcl-2 lacks the signal and therefore localizes to several intracellular membranes. The COOH-terminal region of Bcl-2 can be converted into a targeting signal for the MOM by increasing the basicity surrounding its TM. These data define a new targeting sequence for the MONA and propose that Bcl-2 acts on several intracellular membranes whereas Bcl-x(L) specifically functions on the MOM.
引用
收藏
页码:53 / 64
页数:12
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