Mitochondrial [Ca(2+)] oscillations driven by local high [Ca(2+)] domains generated by spontaneous electric activity.
Mitochondria take up calcium during cell activation thus shaping Ca(2+) signaling and exocytosis. In turn, Ca(2+) uptake by mitochondria increases respiration and ATP synthesis. Targeted aequorins are excellent Ca(2+) probes for subcellular analysis, but single-cell imaging has proven difficult. Here we combine virus-based expression of targeted aequorins with photon-counting imaging to resolve dynamics of the cytosolic, mitochondrial, and nuclear Ca(2+) signals at the single-cell level in anterior pituitary cells. These cells exhibit spontaneous electric activity and cytosolic Ca(2+) oscillations that are responsible for basal secretion of pituitary hormones and are modulated by hypophysiotrophic factors. Aequorin reported spontaneous [Ca(2+)] oscillations in all the three compartments, bulk cytosol, nucleus, and mitochondria. Interestingly, a fraction of mitochondria underwent much larger [Ca(2+)] oscillations, which were driven by local high [Ca(2+)] domains generated by the spontaneous electric activity. These oscillations were large enough to stimulate respiration, providing the basis for local tune-up of mitochondrial function by the Ca(2+) signal.
Villalobos
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Instituto de Biologia y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Cientificas, Departamento de Fisiologia y Bioquimica, Facultad de Medicina, E-47005 Valladolid, Spain.
Núñez
L
L
Chamero
P
P
Alonso
M T
MT
García-Sancho
J
J
D000331:Aequorin / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D020013:Calcium Signaling; D004594:Electrophysiology; D007091:Image Processing, Computer-Assisted; D008163:Luminescent Measurements; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D051381:Rats
D010907:Pituitary Hormones; D000331:Aequorin