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The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore

Author

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  • Jason E. Kokoszka

    (University of California
    Center for Molecular Medicine, Emory University School of Medicine
    Orchid Cellmark)

  • Katrina G. Waymire

    (University of California
    Center for Molecular Medicine, Emory University School of Medicine)

  • Shawn E. Levy

    (Center for Molecular Medicine, Emory University School of Medicine
    Vanderbilt University Medical Center)

  • James E. Sligh

    (Center for Molecular Medicine, Emory University School of Medicine
    Vanderbilt University Medical Center)

  • Jiyang Cai

    (Emory University School of Medicine)

  • Dean P. Jones

    (Emory University School of Medicine)

  • Grant R. MacGregor

    (University of California
    University of California
    Center for Molecular Medicine, Emory University School of Medicine)

  • Douglas C. Wallace

    (University of California
    University of California
    Center for Molecular Medicine, Emory University School of Medicine)

Abstract

A sudden increase in permeability of the inner mitochondrial membrane, the so-called mitochondrial permeability transition, is a common feature of apoptosis and is mediated by the mitochondrial permeability transition pore (mtPTP). It is thought that the mtPTP is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti-apoptotic BAX-BCL2 protein family, cyclophilin D, and the adenine nucleotide (ADP/ATP) translocators (ANTs)1,2. The latter exchange mitochondrial ATP for cytosolic ADP and have been implicated in cell death. To investigate the role of the ANTs in the mtPTP, we genetically inactivated the two isoforms of ANT3,4,5 in mouse liver and analysed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking ANT could still be induced to undergo permeability transition, resulting in release of cytochrome c. However, more Ca2+ than usual was required to activate the mtPTP, and the pore could no longer be regulated by ANT ligands. Moreover, hepatocytes without ANT remained competent to respond to various initiators of cell death. Therefore, ANTs are non-essential structural components of the mtPTP, although they do contribute to its regulation.

Suggested Citation

  • Jason E. Kokoszka & Katrina G. Waymire & Shawn E. Levy & James E. Sligh & Jiyang Cai & Dean P. Jones & Grant R. MacGregor & Douglas C. Wallace, 2004. "The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore," Nature, Nature, vol. 427(6973), pages 461-465, January.
    • Handle: RePEc:nat:nature:v:427:y:2004:i:6973:d:10.1038_nature02229
    DOI: 10.1038/nature02229
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    Cited by:

    1. Lionel Blanchet & Sander Grefte & Jan A M Smeitink & Peter H G M Willems & Werner J H Koopman, 2014. "Photo-Induction and Automated Quantification of Reversible Mitochondrial Permeability Transition Pore Opening in Primary Mouse Myotubes," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-21, November.

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