Elsevier

Cell Calcium

Volume 40, Issues 5–6, November–December 2006, Pages 513-525
Cell Calcium

Calcium microdomains in mitochondria and nucleus

https://doi.org/10.1016/j.ceca.2006.08.013Get rights and content

Abstract

Endomembranes modify the progression of the cytosolic Ca2+ wave and contribute to generate Ca2+ microdomains, both in the cytosol and inside the own organella. The concentration of Ca2+ in the cytosol ([Ca2+]C), the mitochondria ([Ca2+]M) and the nucleus ([Ca2+]N) are similar at rest, but may become very different during cell activation. Mitochondria avidly take up Ca2+ from the high [Ca2+]C microdomains generated during cell activation near Ca2+ channels of the plasma membrane and/or the endomembranes and prevent propagation of the high Ca2+ signal to the bulk cytosol. This shaping of [Ca2+]C signaling is essential for independent regulation of compartmentalized cell functions. On the other hand, a high [Ca2+]M signal is generated selectively in the mitochondria close to the active areas, which tunes up respiration to the increased local needs. The progression of the [Ca2+]C signal to the nucleus may be dampened by mitochondria, the nuclear envelope or higher buffering power inside the nucleoplasm. On the other hand, selective [Ca2+]N signals could be generated by direct release of stored Ca2+ into the nucleoplasm. Ca2+ release could even be restricted to subnuclear domains. Putative Ca2+ stores include the nuclear envelope, their invaginations inside the nucleoplasm (nucleoplasmic reticulum) and nuclear microvesicles. Inositol trisphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate have all been reported to produce release of Ca2+ into the nucleoplasm, but contribution of these mechanisms under physiological conditions is still uncertain.

Section snippets

What are microdomains and how do we evidence them?

Vectorial metabolism was the frame for the chemiosmotic rationale [1]. The term stresses that chemical reactions inside living cells are not dimensionless but have spatial coordinates. The three-dimensional nature of metabolism does also imply that, even at the level of a single-cell, composition may not be homogeneous, but domains with different concentrations of metabolites or ions may coexist. The idea of microscopic hemisphericaldomainscentered upon the active Ca2+ channels was

Mitochondria

Ca2+ transport by mitochondria has received much attention, both because of possible participation in shaping [Ca2+]C signals and because changes of [Ca2+]M are important by themselves for regulation of important cell functions such as respiration or programmed cell death [25]. Ca2+ is taken up by the Ca2+ uniporter, a low-affinity/high capacity system driven by the mitochondrial membrane potential and exits through a Na+/Ca2+ exchanger and also through a Na+-independent system (Fig. 3A) [26],

The functions of nuclear Ca2+

In contrast to mitochondria, nucleus does not act as a Ca2+ sink, but, if anything, the nuclear envelope slows down the propagation of the [Ca2+]C wave to the nucleus [106]. The physiological role of Ca2+ in nuclear signaling may differ in different cells. It has been proposed that [Ca2+]N could control specific nuclear processes such as gene transcription, development, protein transport into the nucleus and cell growth (see ref. [107] for review). A rise in nuclear Ca2+ can regulate gene

Acknowledgements

We thank Mr. Jesús Fernández for technical assistance. This work was funded by grants from the Ministerio de Educación y Ciencia (BFU2004-02765/BFI and BFU2005-05464) and from Junta de Castilla y León (VA016A05). Pablo Chamero holded a predoctoral fellowship from the Basque government.

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