title: Sirtuin-3 modulates Bak- and Bax-dependent apoptosis.
abstract: Sirtuin-3 exhibits properties of a tumor suppressor partly emanating from its ability to control the state of mitochondrial metabolism, with depletion of sirt-3 increasing tumor cell survival. In the present study we demonstrate that depletion of sirtuin-3 brings about an anti-apoptotic phenotype via stimulating cyclophilin-D activity, which promotes the binding of hexokinase II to the mitochondria, thereby preventing Bak/Bax dependent mitochondrial injury and cell death. By contrast, increased expression of sirtuin-3 decreases cyclophilin-D activity, resulting in detachment of hexokinase II from the mitochondria and potentiation of Bak- and Bax-induced mitochondrial injury and loss of cell viability.
authors.affiliation: Department of Molecular Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Verma
authors.forename: Nataly
authors.initials: N
authors.lastname: Shulga
authors.forename: John G
authors.initials: JG
authors.lastname: Pastorino
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D006367:HeLa Cells; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology; D034622:RNA Interference; D017382:Reactive Oxygen Species; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D006593:Hexokinase; D056566:Sirtuin 3; D021983:Cyclophilins; D002945:Cisplatin