Perinuclear, perigranular and sub-plasmalemmal mitochondria have distinct functions in the regulation of cellular calcium transport

We have identified three distinct groups of mitochondria in normal living pancreatic acinar cells, located (i) in the peripheral basolateral region close to the plasma membrane, (ii) around the nucleus and (iii) in the periphery of the granular region separating the granules from the basolateral area. Three-dimensional reconstruction of confocal slices showed that the perigranular mitochondria form a barrier surrounding the whole of the granular region. Cytosolic Ca2+ oscillations initiated in the granular area triggered mitochondrial Ca2+ uptake mainly in the perigranular area. The most intensive uptake occurred in the mitochondria close to the apical plasma membrane, Store-operated Ca2+ influx through the basolateral membrane caused preferential Ca2+ uptake into sub-plasmalemmal mitochondria, The perinuclear mitochondria were activated specifically by local uncaging of Ca2+ in the nucleus. These mitochondria could isolate nuclear and cytosolic Ca2+ signalling. Photobleaching experiments indicated that different groups of mitochondria were not luminally connected. The three mitochondrial groups are activated independently by specific spatiotemporal patterns of cytosolic Ca2+ signals and can therefore participate in the local regulation of Ca2+ homeostasis and energy supply.