Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria.
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.
Department of Molecular Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.
Nataly
N
Shulga
Robin
R
Wilson-Smith
John G
JG
Pastorino
D000107:Acetylation / Q000187:drug effects; D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D003470:Culture Media; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005690:Galactose / Q000494:pharmacology; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D056566:Sirtuin 3 / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D033741:Adenine Nucleotide Translocator 1; D003470:Culture Media; D000081406:Peptidyl-Prolyl Isomerase F; D024101:Mitochondrial Proteins; D006593:Hexokinase; C466093:SIRT3 protein, human; C525357:SIRT4 protein, human; C508544:SIRT5 protein, human; D056566:Sirtuin 3; D037761:Sirtuins; D021983:Cyclophilins; D008239:Lysine; D005690:Galactose