The development of targeted probes (based on the molecular engineering of luminescent or fluorescent proteins) has allowed the specific measure-ment of [Ca 2+ ] in intracellular organelles or cytoplasmic subdomains. This approach gave novel information on different aspects of cellular Ca 2+ homeostasis. Regarding mitochondria, it was possible to demonstrate that, upon physiological stimulation of cells, Ca 2+ is rapidly accumulated in the matrix.