Mitochondria adjust Ca(2+) signaling regime to a pattern of stimulation in salivary acinar cells

The salivary acinar cells have unique Ca(2+) signaling machinery that ensures an extensive secretion. The agonist-induced secretion is governed by Ca(2+) signals originated from the endoplasmic reticulum (ER) followed by a store-operated Ca(2+) entry (SOCE). During tasting and chewing food a frequency of parasympathetic stimulation increases up to ten fold, entailing cells to adapt its Ca(2+) machinery to promote ER refilling and ensure sustained SOCE by yet unknown mechanism. By employing a combination of fluorescent Ca(2+) imaging in the cytoplasm and inside cellular organelles (ER and mitochondria) we described the role of mitochondria in adjustment of Ca(2+) signaling regime and ER refilling according to a pattern of agonist stimulation. Under the sustained stimulation, SOCE is increased proportionally to the degree of ER depletion. Cell adapts its Ca(2+) handling system directing more Ca(2+) into mitochondria via microdomains of high [Ca(2+)] providing positive feedback on SOCE while intra-mitochondrial tunneling provides adequate ER refilling. In the absence of an agonist, the bulk of ER refilling occurs through Ca(2+)-ATPase-mediated Ca(2+) uptake within subplasmalemmal space. In conclusion, mitochondria play a key role in the maintenance of sustained SOCE and adequate ER refilling by regulating Ca(2+) fluxes within the cell that may represent an intrinsic adaptation mechanism to ensure a long-lasting secretion.