The Regulation Mechanism Of Deacetylase Sirt1 To Cell Programmed Necrosis

AIF (apoptosis-inducing factor) is a phylogenetically old flavoprotein normally resides in the mitochondrial intermembrane space, ubiquitous expressed in many kinds of cells and tissues. It is a FAD-dependent NADH oxidoreductase. In normal conditions, AIF is involved in redox activity in mitochondrion and maintains mitochondrial structure.Upon apoptosis induction, AIF is cleaved by calpains and/or cathepsins to yield a soluble protein. The soluble AIF is released from mitochondrion to cytosol, and then translocated to the nucleus where AIF could bind to CypA and rH2AX and causes chromatin condensation,DNA fragmentation (50kbp) in a caspase-independent way and eventually resμlt in cell apoptosis.AIF-mediated apoptosis provides a new target for further understanding the mechanism of apoptosis.Sirtl, the class III hisone deacetylases, is an NAD-dependent histone/non-histone deacetylase,homologous to yeast silence information regμlator 2(Sir2) and is widely distributed in mammalian cells.Sirtl could target a wide range of proteins and regμlate a variety of physiopathological processes,such as cell senescence,apoptosis, neuroprotection, sugar and lipid metabolism,inflammation.In the research,a new Sirtl binding protein was discovered.lt was confirmed that the protein was AIF. Under apoptosis stress, AIF could bind to Sirtl more tightly,endogenous AIF colocalized with endogenous Sirt1.When apoptosis occurs,the acetylation level of AIF was elevated,Sirtl could deacetylate AIF as Sirtl is overexpressed..What’s more,Sirtl could disrupted the combination of AIF and CypA,prevented AIF-mediated DNA fragmentation.