Specific mitochondrial functions in separate sub-cellular domains of pancreatic acinar cells

Abstract

The pancreatic acinar cell synthesizes many digestive proenzymes, which are packaged into secretory (zymogen) granules and secreted by exocytosis upon the action of the neurotransmitter acetylcholine, released from vagal nerve endings, or the hormone cholecystokinin. These secretagogues mobilize Ca(2+) from internal stores and thereby create the cytosolic Ca(2+) signals that control exocytosis. Exocytosis requires Ca(2+), Mg(2+) and ATP. Mg(2+) is present in millimolars concentration throughout the cytosol, but high cytosolic Ca(2+) concentrations need to be created in the local domains near the apical plasma membrane. A special group of mitochondria surrounding the apical granular area play a crucial role in confining cytosolic Ca(2+) elevations to this part of the cell by acting as a Ca(2+) buffer barrier. The Ca(2+) uptake into these mitochondria during apical Ca(2+) spiking stimulates mitochondrial ATP synthesis. ATP is also required for Ca(2+) extrusion via the plasma membrane Ca(2+) pumps, mainly located in the apical area, as well as for Ca(2+) reuptake into the endoplasmic reticulum. Because Ca(2+) extrusion occurs during Ca(2+) spiking, there is a need for compensatory Ca(2+) entry via store-operated Ca(2+) channels. Sub-plasmalemmal (peripheral) mitochondria play an important role in supporting both store-operated Ca(2+) entry at the base as well as the subsequent Ca(2+) pumping into the endoplasmic reticulum. A third group of mitochondria surround the nucleus. They protect the nucleus against unwarranted Ca(2+) signals generated elsewhere and are capable of confining Ca(2+) signals primarily generated inside the nucleus to this part of the cell.