Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate sec
Author: ["Mayte Montero","Maria Teresa Alonso","Estela Carnicero","Inmaculada Cuchillo-Ibáñez","Almudena Albillos","Antonio G. García","Javier García-Sancho","Javier Alvarez"]
Publication: Nature Cell Biology
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Abstract
Activation of calcium-ion (Ca2+) channels on the plasma membrane and on intracellular Ca2+ stores, such as the endoplasmic reticulum, generates local transient increases in the cytosolic Ca2+ concentration that induce Ca2+ uptake by neighbouring mitochondria. Here, by using mitochondrially targeted aequorin proteins with different Ca2+ affinities, we show that half of the chromaffin-cell mitochondria exhibit surprisingly rapid millimolar Ca2+ transients upon stimulation of cells with acetylcholine, caffeine or high concentrations of potassium ions. Our results show a tight functional coupling of voltage-dependent Ca2+ channels on the plasma membrane, ryanodine receptors on the endoplasmic reticulum, and mitochondria. Cell stimulation generates localized Ca2+ transients, with Ca2+ concentrations above 20–40 µM, at these functional units. Protonophores abolish mitochondrial Ca2+ uptake and increase stimulated secretion of catecholamines by three- to fivefold. These results indicate that mitochondria modulate secretion by controlling the availability of Ca2+ for exocytosis.
Cite this article
Montero, M., Alonso, M., Carnicero, E. et al. Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion. Nat Cell Biol 2, 57–61 (2000). https://doi.org/10.1038/35000001