SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining mitochondrial membrane potential and intracellular pH
SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining mitochondrial membrane potential and intracellular pH
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DOI:
10.1038/cdd.2012.62
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发表时间:
2012-11-01
影响因子:
12.4
通讯作者:
Tafani, M.
中科院分区:
文献类型:
--
作者:
Pellegrini, L.;Pucci, B.;Tafani, M.
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 (Delta Psi(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 Delta Psi(mt), intracellular pH and mitochondrial-regulated apoptotic pathways. Cell Death and Differentiation (2012) 19, 1815-1825; doi: 10.1038/cdd.2012.62; published online 18 May 2012