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Research Article

Hexokinase II Detachment from Mitochondria Triggers Apoptosis through the Permeability Transition Pore Independent of Voltage-Dependent Anion Channels

  • Federica Chiara,

    Affiliation: CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, Padova, Italy

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  • Diego Castellaro,

    Affiliation: CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, Padova, Italy

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  • Oriano Marin,

    Affiliation: Department of Biological Chemistry and Venetian Institute of Molecular Medicine (VIMM), University of Padova, Padova, Italy

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  • Valeria Petronilli,

    Affiliation: CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, Padova, Italy

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  • William S. Brusilow,

    Affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America

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  • Magdalena Juhaszova,

    Affiliation: Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America

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  • Steven J. Sollott,

    Affiliation: Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America

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  • Michael Forte,

    Affiliation: Vollum Institute, Oregon Health & Science University, Portland, Oregon, United States of America

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  • Paolo Bernardi mail,

    bernardi@bio.unipd.it (PB); rasola@bio.unipd.it (AR)

    Affiliation: CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, Padova, Italy

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  • Andrea Rasola mail

    bernardi@bio.unipd.it (PB); rasola@bio.unipd.it (AR)

    Affiliation: CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, Padova, Italy

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  • Published: March 19, 2008
  • DOI: 10.1371/journal.pone.0001852

Reader Comments (1)

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Mitochondrial hexokinase association a major determinant of cell death in both cancer and cardiac pathology

Posted by CJZuurbier on 25 Mar 2008 at 15:40 GMT

The article by Chiara and co-workers underlines the general importance of HK binding to mitochondria in the cellular fight against cell death. This may be the mechanism whereby cancer and cardiac diseases come together: We previously showed that many cardioprotective interventions (preconditioning, insulin, morphine) indeed all increase HK association with mitochondria (Zuurbier CJ et al, Am J Physiol 289:H496-499, 2005).
Being a general mechanism for both cancer and cardioprotection, there is the risk that combating the one (e.g. cancer) will increase the incidence of the other (cardiac diseases) and vice versa. Further research will have to take this into account.
For now, the authors are to be congratulated on elucidating in great detail in different models the mechanism whereby HK II detachment from the mitochondria induces cell death.