2007dec caoliuspaper 8sir1自噬nad依赖性脱乙酰酶sirt1在调节中作用见hyelee.pdfVIP

A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy †‡ †§ ¶ In Hye Lee*, Liu Cao*, Raul Mostoslavsky , David B. Lombard , Jie Liu*, Nicholas E. Bruns*, Maria Tsokos , Frederick W. Alt† , and Toren Finkel* *Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; †Howard Hughes Medical ‡ Institute, Children’s Hospital, CBR Institute for Biomedical Research, Harvard University Medical School, Boston, MA 02115; Center for Cancer Research, Massachusetts General Hospital, Harvard University Medical School, Boston, MA 02114; §Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115; and ¶Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Contributed by Frederick W. Alt, December 27, 2007 (sent for review October 22, 2007) We demonstrate a role for the NAD-dependent deacetylase Sirt1 in from nutrient stress. Based on the likely role of both Sirt1 and the regulation of autophagy. In particular, transient reased ex- autophagy in nutrient adaptation and the putative role of both pression of Sirt1 is sufficient to stimulate basal rates of autophagy. In autophagy and Sirt1 in aging and age-related pathologies, we sought addition, we show that Sirt1 / mouse embryonic fibroblasts do not to understand whether there might be a connection between Sirt1 fully activate autophagy under starved conditions. Reconstitution activity and the induction of autophagy. with wild-type but not a deacetylase-inactive mutant of Sirt1 restores autophagy