Mitochondrial [Ca2+] oscillations driven by local high [Ca2+] domains generated by spontaneous electric activity

Mitochondria take up calcium during cell activation thus shaping Ca2+ signa ling and exocytosis. In turn, Ca2+ uptake by mitochondria increases respira tion and ATP synthesis. Targeted aequorins are excellent Ca2+ probes for su bcellular analysis, but single-cell imaging has proven difficult. Here we c ombine virus-based expression of targeted aequorins with photon-counting im aging to resolve dynamics of the cytosolic, mitochondrial, and nuclear Ca2 signals at the single-cell level in anterior pituitary cells. These cells exhibit spontaneous electric activity and cytosolic Ca2+ oscillations that are responsible for basal secretion of pituitary hormones and are modulated by hypophysiotrophic factors. Aequorin reported spontaneous [Ca2+] oscilla tions in all the three compartments, bulk cytosol, nucleus, and mitochondri a. Interestingly, a fraction of mitochondria underwent much larger [Ca2+] o scillations, which were driven by local high [Ca2+] domains generated by th e spontaneous electric activity. These oscillations were large enough to st imulate respiration, providing the basis for local tune-up of mitochondrial function by the Ca2+ signal.