title: Hydrogen peroxide produced inside mitochondria takes part in cell-to-cell transmission of apoptotic signal.
abstract: In monolayer of HeLa cells treated with tumor necrosis factor (TNF), apoptotic cells formed clusters indicating possible transmission of apoptotic signal via the culture media. To investigate this phenomenon, a simple method of enabling two cell cultures to interact has been employed. Two coverslips were placed side by side in a Petri dish, one coverslip covered with apoptogen-treated cells (the inducer) and another with non-treated cells (the recipient). TNF, staurosporine, or H2O2 treatment of the inducer cells is shown to initiate apoptosis on the recipient coverslip. This effect is increased by a catalase inhibitor aminotriazole and is arrested by addition of catalase or by pre-treatment of either the inducer or the recipient cells with nanomolar concentrations of mitochondria-targeted cationic antioxidant MitoQ (10-(6 -ubiquinolyl)decyltriphenylphosphonium), which specifically arrests H2O2-induced apoptosis. The action of MitoQ is abolished by an uncoupler preventing accumulation of MitoQ in mitochondria. It is concluded that reactive oxygen species (ROS) produced by mitochondria in the apoptotic cells initiate the release of H2O2 from these cells. The H2O2 released is employed as a long-distance cell suicide messenger. In processing of such a signal by the recipient cells, mitochondrial ROS production is also involved. It is suggested that the described phenomenon may be involved in expansion of the apoptotic region around a damaged part of the tissue during heart attack or stroke as well as in "organoptosis", i.e. disappearance of organs during ontogenesis.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: O Yu
authors.initials: OY
authors.lastname: Pletjushkina
authors.forename: E K
authors.initials: EK
authors.lastname: Fetisova
authors.forename: K G
authors.initials: KG
authors.lastname: Lyamzaev
authors.forename: O Yu
authors.initials: OY
authors.lastname: Ivanova
authors.forename: L V
authors.initials: LV
authors.lastname: Domnina
authors.forename: M Yu
authors.initials: MY
authors.lastname: Vyssokikh
authors.forename: A V
authors.initials: AV
authors.lastname: Pustovidko
authors.forename: A V
authors.initials: AV
authors.lastname: Alexeevski
authors.forename: D A
authors.initials: DA
authors.lastname: Alexeevski
authors.forename: J M
authors.initials: JM
authors.lastname: Vasiliev
authors.forename: M P
authors.initials: MP
authors.lastname: Murphy
authors.forename: B V
authors.initials: BV
authors.lastname: Chernyak
authors.forename: V P
authors.initials: VP
authors.lastname: Skulachev
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D019311:Staurosporine