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.
Shulga
Nataly
N
Department of Molecular Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.
Wilson-Smith
Robin
R
Pastorino
John G
JG
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