Calcium microdomains in mitochondria and nucleus.

Endomembranes modify the progression of the cytosolic Ca(2+) wave and contribute to generate Ca(2+) microdomains, both in the cytosol and inside the own organella. The concentration of Ca(2+) in the cytosol (Ca(2+)), the mitochondria (Ca(2+)) and the nucleus (Ca(2+)) are similar at rest, but may become very different during cell activation. Mitochondria avidly take up Ca(2+) from the high Ca(2+) microdomains generated during cell activation near Ca(2+) channels of the plasma membrane and/or the endomembranes and prevent propagation of the high Ca(2+) signal to the bulk cytosol. This shaping of Ca(2+) signaling is essential for independent regulation of compartmentalized cell functions. On the other hand, a high Ca(2+) 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 Ca(2+) signal to the nucleus may be dampened by mitochondria, the nuclear envelope or higher buffering power inside the nucleoplasm. On the other hand, selective Ca(2+) signals could be generated by direct release of stored Ca(2+) into the nucleoplasm. Ca(2+) release could even be restricted to subnuclear domains. Putative Ca(2+) 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 Ca(2+) into the nucleoplasm, but contribution of these mechanisms under physiological conditions is still uncertain.