Bax-induced cytochrome c release from mitochondria depends on alpha-helices-5 and -6.

G. Heimlich, Alastair D McKinnon, K. Bernardo, D. Brdiczka, J. C. Reed, Renate Kain, M. Kronke, J. M. Jurgensmeier

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    Abstract

    The pro-apoptotic protein Bax plays a key role in the mitochondrial signalling pathway. Upon induction of apoptosis, Bax undergoes a conformational chan-e and translocates to mitochondrial membranes. where it inserts and mediates the release of cytochrome c from the intermembrane space into the cytosol. However, the domains of Bax that are essential for the induction of cytochrome c release are still elusive. Therefore various Bax deletion mutants were generated and expressed in Escherichia coli. The proteins were then purified in order to delineate the function of the transmembrane domain, the BH3 (Bcl-2 homology 3) domain and the putative pore-fonning alpha-helices-5 and -6. These proteins were used to analyse the mechanism of Bax-induced cytochrome c release from mitochondria. None of the Bax proteins caused cytochrome c release merely through physical perturbation of the mitochondrial outer membrane. The alpha-helices-5 and -6 of Bax were shown to mediate the insertion of the protein into mitochondrial membranes and to be essential for the cytochrome c-releasing activity of Bax. In contrast, neither the transmembrane domain nor a functional BH3 domain is required for the Bax-mediated release of cytochrome c from mitochondria.

    Original languageEnglish
    Pages (from-to)247-255
    Number of pages8
    JournalBiochemical Journal
    Volume378
    Issue number1
    DOIs
    Publication statusPublished - 2004

    Keywords

    • apoptosis
    • Bax
    • Bcl-2
    • cell death
    • cytochrome c
    • mitochondria
    • PROGRAMMED CELL-DEATH
    • PROAPOPTOTIC PROTEIN BAX
    • CHANNEL-FORMING ACTIVITY
    • BCL-2 FAMILY PROTEINS
    • MAMMALIAN-CELLS
    • OUTER-MEMBRANE
    • BH3 DOMAIN
    • IN-VIVO
    • X-L
    • APOPTOSIS

    Cite this

    Heimlich, G., McKinnon, A. D., Bernardo, K., Brdiczka, D., Reed, J. C., Kain, R., Kronke, M., & Jurgensmeier, J. M. (2004). Bax-induced cytochrome c release from mitochondria depends on alpha-helices-5 and -6. Biochemical Journal, 378(1), 247-255. https://doi.org/10.1042/BJ20031152