Mitochondrial calcium signaling driven by the IP3 receptor

Many agonists bring about their effects on cellular functions through a ris e in cytosolic [Ca2+] ([Ca2+](c)) mediated by the second messenger inositol 1,4,5-trisphosphate (IP3). Imaging studies of single cells have demonstrat ed that [Ca2+](c) signals display cell specific spatiotemporal organization that is established by coordinated activation of IP3 receptor Ca2+ channel s. Evidence emerges that cytosolic calcium signals elicited by activation o f the IP3 receptors are efficiently transmitted to the mitochondria. An imp ortant function of mitochondrial calcium signals is to activate the Ca2+-se nsitive mitochondrial dehydrogenases, and thereby to meet demands for incre ased energy in stimulated cells. Activation of the permeability transition pore (PTP) by mitochondrial calcium signals may also be involved in the con trol of cell death. Furthermore, mitochondrial Ca2+ transport appears to mo dulate the spatiotemporal organization of [Ca2+](c) responses evoked by IP3 and so mitochondria may be important in cytosolic calcium signaling as wel l. This paper summarizes recent research to elucidate the mechanisms and si gnificance of IP3-dependent mitochondrial calcium signaling.