title: Redox Nanodomains Are Induced by and Control Calcium Signaling at the ER-Mitochondrial Interface.
abstract: The ER-mitochondrial interface is central to calcium signaling, organellar dynamics, and lipid biosynthesis. The ER and mitochondrial membranes also host sources and targets of reactive oxygen species (ROS), but their local dynamics and relevance remained elusive since measurement and perturbation of ROS at the organellar interface has proven difficult. Employing drug-inducible synthetic ER-mitochondrial linkers, we overcame this problem and demonstrate that the ER-mitochondrial interface hosts a nanodomain of H2O2, which is induced by cytoplasmic [Ca(2+)] spikes and exerts a positive feedback on calcium oscillations. H2O2 nanodomains originate from the mitochondrial cristae, which are compressed upon calcium signal propagation to the mitochondria, likely due to Ca(2+)-induced K(+) and concomitant water influx to the matrix. Thus, ER-mitochondrial H2O2 nanodomains represent a component of inter-organelle communication, regulating calcium signaling and mitochondrial activities.
authors.affiliation: MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Booth
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University, 1444 Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Enyedi
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University, 1444 Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Geiszt
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University, 1444 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Várnai
authors.affiliation: MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: gyorgy.hajnoczky@jefferson.edu.
authors.forename: György
authors.initials: G
authors.lastname: Hajnóczky
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D015220:Calcium Channels; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; D002118:Calcium