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Mitochondrial Calcium Uptake in Activation of the Permeability Transition Pore and Cell Death

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Molecular Basis for Mitochondrial Signaling

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

Mitochondrial permeability transition is a phenomenon of sudden increase in the permeability on the inner membrane in response to excessive calcium accumulation inside the mitochondrial matrix. Permeability transition is caused by the opening of the large nonselective channel – mitochondrial permeability transition pore (mPTP). mPTP opening leads to the depolarization of the mitochondrial membrane and, as a result, to the disruption of the ATP synthesis. Prevention of mPTP is protective against stress induced cell death, which makes it a potentially important pharmacological target. Here we review current opinions regarding the molecular structure of mPTP and mechanisms of its activation by calcium. We discuss the importance of calcium-phosphate interactions in the process of mPTP activation. Further we review recently proposed models of mPTP formation that involve participation of the oligomers of the C subunit of the mitochondrial ATP synthase and discuss potential roles of inorganic polyphosphate and calcium in transition of the C subunit oligomers into mPTP channel. Finally, we review potential physiological roles of mPTP.

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Acknowledgments

Authors would like to acknowledge the support from the American Heart Association and from the National Institute of Health.

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Authors and Affiliations

  1. Department of Basic Sciences, New York University, College of Dentistry, 345 East 24th Street, Schwartz Building, Room 1030, New York, NY, 10010, USA

    Maria E. Solesio & Evgeny V. Pavlov

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  1. Maria E. Solesio
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  2. Evgeny V. Pavlov
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Correspondence to Evgeny V. Pavlov .

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  1. Section on Molecular Transport, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

    Tatiana K. Rostovtseva

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Solesio, M.E., Pavlov, E.V. (2017). Mitochondrial Calcium Uptake in Activation of the Permeability Transition Pore and Cell Death. In: Rostovtseva, T. (eds) Molecular Basis for Mitochondrial Signaling. Biological and Medical Physics, Biomedical Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-55539-3_4

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