ATP increases within the lumen of the endoplasmic reticulum upon intracellular Ca2+ release |
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Authors: | Neelanjan Vishnu Muhammad Jadoon Khan Felix Karsten Lukas N Groschner Markus Waldeck-Weiermair Rene Rost Seth Hallstr?m Hiromi Imamura Wolfgang F Graier Roland Malli |
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Institution: | Carnegie Mellon University;aInstitute of Molecular Biology and Biochemistry, Center of Physiological Medicine, Medical University of Graz, 8010 Graz, Austria;bInstitute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, 8010 Graz, Austria;cPrecursory Research for Embryonic Science, Japan Science and Technology Agency, Tokyo 102-0075, Japan |
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Abstract: | Multiple functions of the endoplasmic reticulum (ER) essentially depend on ATP within this organelle. However, little is known about ER ATP dynamics and the regulation of ER ATP import. Here we describe real-time recordings of ER ATP fluxes in single cells using an ER-targeted, genetically encoded ATP sensor. In vitro experiments prove that the ATP sensor is both Ca2+ and redox insensitive, which makes it possible to monitor Ca2+-coupled ER ATP dynamics specifically. The approach uncovers a cell type–specific regulation of ER ATP homeostasis in different cell types. Moreover, we show that intracellular Ca2+ release is coupled to an increase of ATP within the ER. The Ca2+-coupled ER ATP increase is independent of the mode of Ca2+ mobilization and controlled by the rate of ATP biosynthesis. Furthermore, the energy stress sensor, AMP-activated protein kinase, is essential for the ATP increase that occurs in response to Ca2+ depletion of the organelle. Our data highlight a novel Ca2+-controlled process that supplies the ER with additional energy upon cell stimulation. |
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