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Mitochondrial Ca2+ homeostasis: mechanism, role, and tissue specificities

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Abstract

Mitochondria from every tissue are quite similar in their capability to accumulate Ca2+ in a process that depends on the electrical potential across the inner membrane; it is catalyzed by a gated channel (named mitochondrial Ca2+ uniporter), the molecular identity of which has only recently been unraveled. The release of accumulated Ca2+ in mitochondria from different tissues is, on the contrary, quite variable, both in terms of speed and mechanism: a Na+-dependent efflux in excitable cells (catalyzed by NCLX) and a H+/Ca2+ exchanger in other cells. The efficacy of mitochondrial Ca2+ uptake in living cells is strictly dependent on the topological arrangement of the organelles with respect to the source of Ca2+ flowing into the cytoplasm, i.e., plasma membrane or intracellular channels. In turn, the structural and functional relationships between mitochondria and other cellular membranes are dictated by the specific architecture of different cells. Mitochondria not only modulate the amplitude and the kinetics of local and bulk cytoplasmic Ca2+ changes but also depend on the Ca2+ signal for their own functionality, in particular for their capacity to produce ATP. In this review, we summarize the processes involved in mitochondrial Ca2+ handling and its integration in cell physiology, highlighting the main common characteristics as well as key differences, in different tissues.

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Acknowledgments

The original data by the authors have been supported by grants from the Italian National Research Council (CNR), the MIUR projects PRIN and FIRB, the Italian Institute of Technology (IIT), the Veneto Region and the University of Padua to TP and PP. We are grateful to Dr. P. Magalhaes for critically revising the manuscript and to Dr. D. De Stefani for unpublished information on MCU physiology and structure.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Padua, Padua, Italy

    Paola Pizzo, Ilaria Drago, Riccardo Filadi & Tullio Pozzan

  2. CNR Institute of Neuroscience, Viale G. Colombo 3, 35121, Padua, Italy

    Tullio Pozzan

  3. Venetian Institute of Molecular Medicine, Padua, Italy

    Tullio Pozzan

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  1. Paola Pizzo
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  2. Ilaria Drago
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  3. Riccardo Filadi
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  4. Tullio Pozzan
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Correspondence to Tullio Pozzan.

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This article is published as part of the special issue on “Cell-specific roles of mitochondrial Ca2+ handling.”

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Pizzo, P., Drago, I., Filadi, R. et al. Mitochondrial Ca2+ homeostasis: mechanism, role, and tissue specificities. Pflugers Arch - Eur J Physiol 464, 3–17 (2012). https://doi.org/10.1007/s00424-012-1122-y

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