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.
Tafani, M.
中科院分区:
生物学1区
文献类型:
--
作者:
Pellegrini, L.;Pucci, B.;Tafani, M.

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线粒体sirtuin 3 (SIRT3)介导细胞抵抗各种形式的应激。在这里,我们发现,在哺乳动物细胞缺氧和staurosporine处理SIRT3防止线粒体膜电位(Delta Psi(mt))的损失,细胞内酸化和活性氧的积累。我们的研究结果表明:(i) SIRT3通过阻止HKII与线粒体结合来抑制线粒体的通透性转变和膜电位的丧失;(ii) SIRT3增加线粒体碳酸酐酶VB的催化活性,从而防止细胞内酸化、Bax活化和凋亡细胞死亡。总之,我们提出,在哺乳动物细胞中,SIRT3在连接Delta Psi(mt),细胞内pH和线粒体调节的凋亡途径的变化中起核心作用。细胞死亡与分化(2012)19,1815 -1825;doi: 10.1038 / cdd.2012.62;2012年5月18日在线发布
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