title: Synchronism in mitochondrial ROS flashes, membrane depolarization and calcium sparks in human carcinoma cells.
abstract: Mitochondria are major producers of reactive oxygen species (ROS) in many cells including cancer cells. However, complex interrelationships between mitochondrial ROS (mitoROS), mitochondrial membrane potential (ΔΨm) and Ca2+are not completely understood. Using human carcinoma cells, we further highlight biphasic ROS dynamics: - gradual mitoROS increase followed by mitoROS flash. Also, we demonstrate heterogeneity in rates of mitoROS generation and flash initiation time. Comparing mitochondrial and near-extra-mitochondrial signals, we show that mechanisms of mitoROS flashes in single mitochondria, linked to mitochondrial permeability transition pore opening (ΔΨm collapse) and calcium sparks, may involve flash triggering by certain levels of external ROS released from the same mitochondria. In addition, mitochondria-mitochondria interactions can produce wave propagations of mitoROS flashes and ΔΨm collapses in cancer cells similar to phenomena of ROS-induced ROS release (RIRR). Our data suggest that in cancer cells RIRR, activation of mitoROS flashes and mitochondrial depolarization may involve participation of extramitochondrial-ROS produced either by individual mitochondria and/or by neighboring mitochondria. This could represent general mechanisms in ROS-ROS signaling with suggested role in both mitochondrial and cellular physiology and signaling.
authors.affiliation: Cardiac Surgery Laboratory, Department of Heart Surgery, Medical University of Innsbruck, Innsbruck A-6020, Austria. Electronic address: andrey.kuznetsov@tirol-kliniken.at.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kuznetsov
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR 00936-5067, USA.
authors.forename: Sabzali
authors.initials: S
authors.lastname: Javadov
authors.affiliation: Laboratory of Fundamental and Applied Bioenergetics, INSERM U884, University Joseph Fourier, Grenoble, France.
authors.forename: Valdur
authors.initials: V
authors.lastname: Saks
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Raimund
authors.initials: R
authors.lastname: Margreiter
authors.affiliation: Cardiac Surgery Laboratory, Department of Heart Surgery, Medical University of Innsbruck, Innsbruck A-6020, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000975:Antioxidants / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology; D005452:Fluoresceins / Q000737:chemistry; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress; D010777:Photochemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry; D059010:Single-Cell Analysis; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005452:Fluoresceins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D012235:Rhodamines; C401833:tetramethylrhodamine methyl ester; C029569:diacetyldichlorofluorescein; D016572:Cyclosporine; D013482:Superoxide Dismutase
keywords: Ca(2+) sparks; Carcinoma cells; Membrane potential; Mitochondria; ROS flashes