SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining mitochondrial membrane potential and intracellular pH |
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| Authors: | L Pellegrini B Pucci L Villanova M L Marino G Marfe L Sansone E Vernucci D Bellizzi V Reali M Fini M A Russo M Tafani |
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| Institution: | 1.Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy;2.Department of Cellular and Molecular Pathology, IRCCS San Raffaele Pisana, Rome, Italy;3.Department of Therapeutic Research and Medicines Evaluation, Unit of Antitumor Drugs, Istituto Superiore di Sanità, Rome, Italy;4.Department of Experimental Medicine and Biochemical Sciences, University of Rome ‘Tor Vergata'', Rome, Italy;5.Department of Cell Biology, University of Calabria, Rende, Italy |
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| Abstract: | Mitochondrial sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. Here, we show that in mammalian cells subjected to hypoxia and staurosporine treatment SIRT3 prevents loss of mitochondrial membrane potential (ΔΨmt), intracellular acidification and reactive oxygen species accumulation. Our results indicate that: (i) SIRT3 inhibits mitochondrial permeability transition and loss of membrane potential by preventing HKII binding to the mitochondria, (ii) SIRT3 increases catalytic activity of the mitochondrial carbonic anhydrase VB, thereby preventing intracellular acidification, Bax activation and apoptotic cell death. In conclusion we propose that, in mammalian cells, SIRT3 has a central role in connecting changes in ΔΨmt, intracellular pH and mitochondrial-regulated apoptotic pathways. |
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| Keywords: | SIRT3 mitochondria ROS intracellular pH |
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