tailieunhanh - Báo cáo khoa học: Metabolic control of mitochondrial properties by adenine nucleotide translocator determines palmitoyl-CoA effects Implications for a mechanism linking obesity and type 2 diabetes

Inhibition of the mitochondrial adenine nucleotide translocator (ANT) by long-chain acyl-CoA esters has been proposed to contribute to cellular dys-function in obesity and type 2 diabetes by increasing formation of reactive oxygen species and adenosine via effects on the coenzyme Q redox state, mitochondrial membrane potential (Dw) and cytosolic ATP concentrations. | ễFEBS Journal Metabolic control of mitochondrial properties by adenine nucleotide translocator determines palmitoyl-CoA effects Implications for a mechanism linking obesity and type 2 diabetes Jolita Ciapaite1 5 Stephan J. L. Bakker2 Michaela Diamant3 Gerco van Eikenhorst1 Robert J. Heine3 Hans V. Westerhoff1 4 and Klaas Krab1 1 Department of Molecular CellPhysiology Institute for Molecular Cell Biology Faculty of Earth and Life Sciences VU University Amsterdam the Netherlands 2 Department of InternalMedicine University of Groningen and University MedicalCenter Groningen the Netherlands 3 Department of Endocrinology Institute for Cardiovascular Research VU University MedicalCenter Amsterdam the Netherlands 4 Manchester Centre for Integrative Systems Biology MIB University of Manchester UK 5 Centre of EnvironmentalResearch Faculty of Nature Sciences Vytautas Magnus University Kaunas Lithuania Keywords metabolic control analysis oxidative phosphorylation palmitoyl-CoA reactive oxygen species type 2 diabetes Correspondence J. Ciapaite Centre of Environmental Research Faculty of Nature Sciences Vytautas Magnus University Kaunas Vileikos 8 LT-44404 Lithuania Fax 370 37 327904 Tel 370 37 327905 E-mail Received 21 June 2006 revised 19 August 2006 accepted 4 October 2006 doi Inhibition of the mitochondrial adenine nucleotide translocator ANT by long-chain acyl-CoA esters has been proposed to contribute to cellular dysfunction in obesity and type 2 diabetes by increasing formation of reactive oxygen species and adenosine via effects on the coenzyme Q redox state mitochondrial membrane potential DW and cytosolic ATP concentrations. We here show that 5 M palmitoyl-CoA increases the ratio of reduced to oxidized coenzyme Q QH2 Q by 42 9 AW by 13 1 mV 9 and the intramitochondrial ATP ADP ratio by 352 34 and decreases the extramitochondrial ATP ADP ratio by 63 4 in actively phosphorylating mitochondria. The latter .