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The permeability transition pore as a mitochondrial calcium release channel: A critical appraisal

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Abstract

Mitochondria from a variety of sources possess an inner membrane channel, the permeability transition pore. The pore is a voltage-dependent channel, activated by matrix Ca2+ and inhibited by matrix H+, which can be blocked by cyclosporin A, presumably after binding to mitochondrial cyclophilin. The physiological function of the permeability transition pore remains unknown. Here we evaluate its potential role as a fast Ca2+ release channel involved in mitochondrial and cellular Ca2+ homeostasis. We (i) discuss the theoretical and experimental reasons why mitochondria need a fast, inducible Ca2+ release channel; (ii) analyze the striking analogies between the mitochondrial permeability transition pore and the sarcoplasmic reticulum ryanodine receptor-Ca2+ release channel; (iii) argue that the permeability transition pore can act as a selective release channel for Ca2+ despite its apparent lack of selectivity for the transported speciesin vitro; and (iv) discuss the importance of mitochondria in cellular Ca2+ homeostasis, and how disruption of this function could impinge upon cell viability, particularly under conditions of oxidative stress.

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  1. CNR Unit for the Study of Biomembranes and the Laboratory of Biophysics and Membrane Biology, Department of Biomedical Sciences, University of Padova, Italy

    Paolo Bernardi & Valeria Petronilli

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  1. Paolo Bernardi
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  2. Valeria Petronilli
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Bernardi, P., Petronilli, V. The permeability transition pore as a mitochondrial calcium release channel: A critical appraisal. J Bioenerg Biomembr 28, 131–138 (1996). https://doi.org/10.1007/BF02110643

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  • DOI: https://doi.org/10.1007/BF02110643

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