SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining mitochondrial membrane potential and intracellular pH

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

Research output: Contribution to journalArticle

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 (ΔΨ mt), 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.

Original languageEnglish
Pages (from-to)1815-1825
Number of pages11
JournalCell Death and Differentiation
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Keywords

  • intracellular pH
  • mitochondria
  • ROS
  • SIRT3

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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