The N-terminal End of Bax Contains a Mitochondrial-targeting Signal

The translocation of Bax α, 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 (NT) end of Bax α, which contains its first α helix (Ηα1), is a functional mitochondrial-addressing signal bot...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of biological chemistry 2003-03, Vol.278 (13), p.11633-11641
Hauptverfasser: Cartron, Pierre-François, Priault, Muriel, Oliver, Lisa, Meflah, Khaled, Manon, Stephen, Vallette, François M
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The translocation of Bax α, 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 (NT) end of Bax α, which contains its first α helix (Ηα1), 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 ψ, which lacks the first 20 amino acids of Bax α and is constitutively associated with mitochondria. Deletion of Ηα1 impairs the binding of Bax ψ to mitochondria, whereas a fusion of the N terminus of Bax α, which contains Ηα1 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 ψ with mitochondria as well as Bax-apoptogenic properties. The mutations of the Ηα1, which inhibit Bax α and Bax ψ translocation to mitochondria, also block the subsequent activation of the execution phase of apoptosis. Conversely, a deletion of the C terminus does not appear to influence Bax α and Bax ψ mitochondrial addressing. Taken together, our results suggest that Bax is targeted to mitochondria by its NT and thus through a pathway that is unique for a member of the BCL-2 family.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M208955200