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 p ancreatic acinar cells, located (i) in the peripheral basolateral region cl ose to the plasma membrane, (ii) around the nucleus and (iii) in the periph ery of the granular region separating the granules from the basolateral are a. Three-dimensional reconstruction of confocal slices showed that the peri granular mitochondria form a barrier surrounding the whole of the granular region. Cytosolic Ca2+ oscillations initiated in the granular area triggere d mitochondrial Ca2+ uptake mainly in the perigranular area. The most inten sive uptake occurred in the mitochondria close to the apical plasma membran e, Store-operated Ca2+ influx through the basolateral membrane caused prefe rential Ca2+ uptake into sub-plasmalemmal mitochondria, The perinuclear mit ochondria were activated specifically by local uncaging of Ca2+ in the nucl eus. These mitochondria could isolate nuclear and cytosolic Ca2+ signalling . Photobleaching experiments indicated that different groups of mitochondri a were not luminally connected. The three mitochondrial groups are activate d independently by specific spatiotemporal patterns of cytosolic Ca2+ signa ls and can therefore participate in the local regulation of Ca2+ homeostasi s and energy supply.