Ca2+ As a Second Messenger within Mitochondria of the Heart and other Tissues

Many hormones and other external stimuli influence intramitochondrial metabolism (25). The mechanisms by which this occurs involve not only signal transmission across the plasma membrane but also across the inner membrane of mitochondria. This latter membrane is essentially impermeable to all charged molecules unless a specific carrier or transport system is present in the membrane. Of the known second-messenger molecules that act within the cytosolic compartment of mammalian cells, it appears that only Ca2+ is transferred into the mitochondrial matrix. The Ca2+ -transport system in the inner membrane of mitochondria (Figure 1) has separate uptake and efflux components (for reviews see 9, 14, 70). Uptake of Ca2+ occurs via an electrophoretic uniporter driven by the large electrical potential across the inner membrane. This process is inhibited by the dye ruthenium red and also by Mg2+ at concentrations likely to be present in the cytoplasm of cells (i.e. about 1 mM). The transfer of Ca2+ out of the mitochondria in heart and many other tissues occurs mainly via an e1ec-