Department of Molecular Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.
J Cell Sci. 2010 Mar 15;123(Pt 6):894-902. doi: 10.1242/jcs.061846. Epub 2010 Feb 16.
We demonstrate that the transition from a reliance on glycolysis to oxidative phosphorylation in a transformed cell line is dependent on an increase in the levels and activity of sirtuin-3. Sirtuin-3 deacetylates cyclophilin D, diminishing its peptidyl-prolyl cis-trans isomerase activity and inducing its dissociation from the adenine nucleotide translocator. Moreover, the sirtuin-3-induced inactivation of cyclophilin D causes a detachment of hexokinase II from the mitochondria that is necessary for stimulation of oxidative phosphorylation. These results might have important implications for the role of sirtuin-3 in the metabolism of some cancer cells and their susceptibility to mitochondrial injury and cytotoxicity.
我们证明，在转化细胞系中，从依赖糖酵解向氧化磷酸化的转变取决于烟酰胺腺嘌呤二核苷酸（NAD+）依赖性去乙酰化酶 sirtuin-3 水平和活性的增加。Sirtuin-3 去乙酰化环孢素 D，降低其肽基脯氨酰顺反异构酶活性，并诱导其从腺嘌呤核苷酸转运蛋白上解离。此外，sirtuin-3 诱导的环孢素 D 失活导致己糖激酶 II 从线粒体上脱离，这对于刺激氧化磷酸化是必需的。这些结果可能对 sirtuin-3 在某些癌细胞的代谢及其对线粒体损伤和细胞毒性的易感性中的作用具有重要意义。
