title: VDAC electronics: 3. VDAC-Creatine kinase-dependent generation of the outer membrane potential in respiring mitochondria.
abstract: Mitochondrial energy in cardiac cells has been reported to be channeled into the cytosol through the intermembrane contact sites formed by the adenine nucleotide translocator, creatine kinase and VDAC. Computational analysis performed in this study showed a high probability of the outer membrane potential (OMP) generation coupled to such a mechanism of energy channeling in respiring mitochondria. OMPs, positive inside, calculated at elevated concentrations of creatine are high enough to restrict ATP release from mitochondria, to significantly decrease the apparent K(m,ADP) for state 3 respiration and to maintain low concentrations of Ca(2+) in the mitochondrial intermembrane space. An inhibition by creatine of Ca(2+)-induced swelling of isolated mitochondria and other protective effects of creatine reported in the literature might be explained by generated positive OMP. We suggest that VDAC-creatine kinase-dependent generation of OMP represents a novel physiological factor controlling metabolic state of mitochondria, cell energy channeling and resistance to death.
authors.affiliation: Escuela de Física, Facultad de Ciencias, Universidad Nacional de Colombia, sede Medellín, Calle 59A, No 63-20, Medellín, Colombia. Electronic address: vvasilie@unal.edu.co.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Lemeshko
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival; D003401:Creatine / Q000378:metabolism / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: D050994:Voltage-Dependent Anion Channels; D003402:Creatine Kinase; D003401:Creatine; D010100:Oxygen; D002118:Calcium
keywords: Calcium; Creatine; Creatine kinase; Membrane potential; Mitochondrial outer membrane; VDAC