The N-terminal end of bax contains a mitochondrial-targeting signal. .
Cartron PF, Priault M, Oliver L, Meflah K, Manon S, Vallette FM
Journal of Biological Chemistry (2003)
Category: apoptosis ¤ Added: Jan 20, 2003 ¤ Rating: ◊◊
The translocation of Bax alpha, a pro-apoptotic member of the BCL-2 family from the cytosol to mitochondria is a central event of the apoptotic program. We report here that the N-terminal end of Bax alpha which contains its first alpha helix (Ha1) is a functional mitochondrial-addressing signal both in mammals and in yeast. Similar results were obtained with a newly described variant of Bax, called Bax psi, which lacks the first 20 amino acids of Bax alpha and is constitutively associated with mitochondria. Deletion of Ha1 impairs the binding of Bax psi to mitochondria while a fusion of the NH2-terminal (NT) of Bax alpha which contains Ha1 with a cytosolic protein results in the binding of the chimeric proteins to mitochondria both in a cell free assay and in vitro. More importantly, the mitochondria bound chimeric proteins inhibit the interaction of Bax psi with mitochondria as well as Bax apoptogenic properties. Mutations of the Ha1 which inhibit Bax alpha and Bax psi translocation to mitochondria also block the subsequent activation of the execution phase of apoptosis. Conversely, a deletion of the C-terminus (CT) does not appear to influence Bax alpha and Bax psimitochondrial addressing. Taken together, our results suggest that Bax is targeted to mitochondria by its NT and thus through a pathway which is unique for a member of the BCL-2 family.
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