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Conformation of the Bax C-terminus regulates subcellular location and cell death.

Author information

Affiliations

  • 1. Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
      Authors
    • Nechushtan A 1
    (1 author)

The EMBO Journal, 01 May 1999, 18(9):2330-2341
https://doi.org/10.1093/emboj/18.9.2330 PMID: 10228148 PMCID: PMC1171316

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Abstract 

Bax, a pro-apoptotic member of the Bcl-2 family, translocates from the cytosol to the mitochondria during programmed cell death. We report here that both gain-of-function and loss-of-function mutations can be achieved by altering a single amino acid in the Bax hydrophobic C-terminus. The properly mutated C-terminus of Bax can target a non-relevant protein to the mitochondria, showing that specific conformations of this domain alone allow mitochondrial docking. These data along with N-terminus epitope exposure experiments suggest that the C- and the N-termini interact and that upon triggering of apoptosis, Bax changes conformation, exposing these two domains to insert into the mitochondria and regulate the cell death machinery.

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Logo of embojLink to Publisher's site
EMBO J. 1999 May 4; 18(9): 2330–2341.
PMCID: PMC1171316
PMID: 10228148

Conformation of the Bax C-terminus regulates subcellular location and cell death.

A Nechushtan, C L Smith, Y T Hsu, and R J Youle
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Abstract

Bax, a pro-apoptotic member of the Bcl-2 family, translocates from the cytosol to the mitochondria during programmed cell death. We report here that both gain-of-function and loss-of-function mutations can be achieved by altering a single amino acid in the Bax hydrophobic C-terminus. The properly mutated C-terminus of Bax can target a non-relevant protein to the mitochondria, showing that specific conformations of this domain alone allow mitochondrial docking. These data along with N-terminus epitope exposure experiments suggest that the C- and the N-termini interact and that upon triggering of apoptosis, Bax changes conformation, exposing these two domains to insert into the mitochondria and regulate the cell death machinery.

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Selected References

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