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 language | English |
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Pages (from-to) | 1815-1825 |
Number of pages | 11 |
Journal | Cell Death and Differentiation |
Volume | 19 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2012 |
Keywords
- intracellular pH
- mitochondria
- ROS
- SIRT3
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology