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Mitochondria and Cell Death pp 1–15Cite as

Lethal and Nonlethal Functions of the Permeability Transition Pore

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Part of the book series: Cell Death in Biology and Diseases ((CELLDEATH))

Abstract

The mitochondrial permeability transition is an inner membrane permeability increase that can be traced to the opening of a specific but nonselective high-conductance inner membrane channel named the permeability transition pore (PTP). PTP can open either transiently or permanently. There is an abundant literature from different laboratories using cellular or animal models, showing that PTP inhibition prevents some types of cell death. Although permanent PTP opening allows the release of mitochondrial pro-apoptotic proteins, the mechanism for release remains debated. Contrary to permanent PTP opening, transient PTP opening does not induce cell death and may have physiological functions. The best-characterized nonlethal function of PTP may be participation in calcium homeostasis, which is supported by limited but convincing evidence. Transient PTP opening may also participate in the phenomenon named ROS-induced ROS release and also serve in the uptake-release of compounds that lack a specific transport system in the inner membrane and are present both in matrix and cytosol at similar concentrations. Finally, transient PTP opening might allow ATP production by succinate-CoA ligase inside mitochondria when excess NADH inhibits the TCA cycle.

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Authors and Affiliations

  1. University Grenoble Alpes, LBFA, Grenoble, 38000, France

    Eric Fontaine

  2. INSERM, U1055, Grenoble, 38000, France

    Eric Fontaine

  3. Department of Biomedical Sciences, Consiglio Nazionale delle Ricerche Neuroscience Institute, University of Padova, Padova, 35121, Italy

    Paolo Bernardi

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  1. Eric Fontaine
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  2. Paolo Bernardi
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Correspondence to Eric Fontaine .

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  1. Clinical Research Divison, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    David M. Hockenbery

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Fontaine, E., Bernardi, P. (2016). Lethal and Nonlethal Functions of the Permeability Transition Pore. In: Hockenbery, D. (eds) Mitochondria and Cell Death. Cell Death in Biology and Diseases. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3612-0_1

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