40
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Although programmed cell death (PCD) is extensively studied in multicellular organisms, in recent years it has been shown that a unicellular organism, yeast Saccharomyces cerevisiae, also possesses death program(s). In particular, we have found that a high doses of yeast pheromone is a natural stimulus inducing PCD. Here, we show that the death cascades triggered by pheromone and by a drug amiodarone are very similar. We focused on the role of mitochondria during the pheromone/amiodarone-induced PCD. For the first time, a functional chain of the mitochondria-related events required for a particular case of yeast PCD has been revealed: an enhancement of mitochondrial respiration and of its energy coupling, a strong increase of mitochondrial membrane potential, both events triggered by the rise of cytoplasmic [Ca 2+], a burst in generation of reactive oxygen species in center o of the respiratory chain complex III, mitochondrial thread-grain transition, and cytochrome c release from mitochondria. A novel mitochondrial protein required for thread-grain transition is identified.

          Related collections

          Most cited references63

          • Record: found
          • Abstract: found
          • Article: not found

          Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked.

          Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in response to a variety of stimuli. Cytosolic cytochrome c is necessary for the initiation of the apoptotic program, suggesting a possible connection between Bcl-2 and cytochrome c, which is normally located in the mitochondrial intermembrane space. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria. Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Molecular characterization of mitochondrial apoptosis-inducing factor.

            Mitochondria play a key part in the regulation of apoptosis (cell death). Their intermembrane space contains several proteins that are liberated through the outer membrane in order to participate in the degradation phase of apoptosis. Here we report the identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei. AIF is a flavoprotein of relative molecular mass 57,000 which shares homology with the bacterial oxidoreductases; it is normally confined to mitochondria but translocates to the nucleus when apoptosis is induced. Recombinant AIF causes chromatin condensation in isolated nuclei and large-scale fragmentation of DNA. It induces purified mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Microinjection of AIF into the cytoplasm of intact cells induces condensation of chromatin, dissipation of the mitochondrial transmembrane potential, and exposure of phosphatidylserine in the plasma membrane. None of these effects is prevented by the wide-ranging caspase inhibitor known as Z-VAD.fmk. Overexpression of Bcl-2, which controls the opening of mitochondrial permeability transition pores, prevents the release of AIF from the mitochondrion but does not affect its apoptogenic activity. These results indicate that AIF is a mitochondrial effector of apoptotic cell death.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria.

              Formation of H2O2 has been studied in rat heart mitochondria, pretreated with H2O2 and aminotriazole to lower their antioxidant capacity. It is shown that the rate of H2O2 formation by mitochondria oxidizing 6 mM succinate is inhibited by a protonophorous uncoupler, ADP and phosphate, malonate, rotenone and myxothiazol, and is stimulated by antimycin A. The effect of ADP is abolished by carboxyatractylate and oligomycin. Addition of uncoupler after rotenone induces further inhibition of H2O2 production. Inhibition of H2O2 formation by uncoupler, malonate and ADP+Pi is shown to be proportional to the delta psi decrease by these compounds. A threshold delta psi value is found, above which a very strong increase in H2O2 production takes place. This threshold slightly exceeds the state 3 delta psi level. The data obtained are in line with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169-2021 that a high proton motive force in state 4 is potentially dangerous for the cell due to an increase in the probability of superoxide formation.
                Bookmark

                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                17 January 2005
                : 168
                : 2
                : 257-269
                Affiliations
                [1 ]Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
                [2 ]A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia
                [3 ]BioTechnological Center, Proteomics and Cellular Machines, University of Technology Dresden, D-01307 Dresden, Germany
                Author notes

                Correspondence to Fedor F. Severin: severin@ 123456mpi-cdg.de

                Article
                200408145
                10.1083/jcb.200408145
                2171581
                15657396
                f52f8cc8-801a-42b7-b929-c86d34047624
                Copyright © 2005, The Rockefeller University Press
                History
                : 24 August 2004
                : 30 November 2004
                Categories
                Research Articles
                Article

                Cell biology
                Cell biology

                Comments

                Comment on this article