title: ATP increases within the lumen of the endoplasmic reticulum upon intracellular Ca2+ release.
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 Ca(2+) and redox insensitive, which makes it possible to monitor Ca(2+)-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 Ca(2+) release is coupled to an increase of ATP within the ER. The Ca(2+)-coupled ER ATP increase is independent of the mode of Ca(2+) 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 Ca(2+) depletion of the organelle. Our data highlight a novel Ca(2+)-controlled process that supplies the ER with additional energy upon cell stimulation.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Physiological Medicine, Medical University of Graz, 8010 Graz, Austria Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, 8010 Graz, Austria Precursory Research for Embryonic Science, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Neelanjan
authors.initials: N
authors.lastname: Vishnu
authors.forename: Muhammad
authors.initials: M
authors.lastname: Jadoon Khan
authors.forename: Felix
authors.initials: F
authors.lastname: Karsten
authors.forename: Lukas N
authors.initials: LN
authors.lastname: Groschner
authors.forename: Markus
authors.initials: M
authors.lastname: Waldeck-Weiermair
authors.forename: Rene
authors.initials: R
authors.lastname: Rost
authors.forename: Seth
authors.initials: S
authors.lastname: Hallström
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamura
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Graier
authors.forename: Roland
authors.initials: R
authors.lastname: Malli
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D010084:Oxidation-Reduction; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats
chemical_list: D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D002118:Calcium