Long-term modulation of mitochondrial Ca(2+) signals by protein kinase C isozymes

The modulation of Ca(2+) signaling patterns during repetitive stimulations represents an important mechanism for integrating through time the inputs received by a cell. By either overexpressing the isoforms of protein kinase C (PKC) or inhibiting them with specific blockers, we investigated the role of this family of proteins in regulating the dynamic interplay of the intracellular Ca(2+) pools. The effects of the different isoforms spanned from the reduction of ER Ca(2+) release (PKCα) to the increase or reduction of mitochondrial Ca(2+) uptake (PKCζ and PKCβ/PKCδ, respectively). This PKC-dependent regulatory mechanism underlies the process of mitochondrial Ca(2+) desensitization, which in turn modulates cellular responses (e.g., insulin secretion). These results demonstrate that organelle Ca(2+) homeostasis (and in particular mitochondrial processing of Ca(2+) signals) is tuned through the wide molecular repertoire of intracellular Ca(2+) transducers.