title: Cyclical mitochondrial deltapsiM fluctuations linked to electron transport, F0F1 ATP-synthase and mitochondrial Na+/Ca+2 exchange are reduced in Alzheimer's disease cybrids.
abstract: Reduced complex IV, increased oxidative stress and beta amyloid peptide secretion in Alzheimer's disease (AD) can be replicated in cybrid models. We characterized cyclical mitochondrial deltapsiM fluctuations ('flickering') in neuroblastoma cells and AD/CTL cybrids. Flickering was blocked by ATP-synthase inhibition, was not observed in rho0 cells and was not blocked by antioxidant treatment. Flickering was not affected by the Ca(+2) uniporter antagonist Ru360 but was eliminated by BAPTA or CGP37137 blockade of the mitochondrial Na(+)/Ca(+2) exchanger. AD cybrid mitochondria showed reduced flickering. Flickering seems to represent coupling of deltapsiM to F0F1 ATP-synthase; reduction of flickering in AD cybrids suggests dysfunction of this coupling.
authors.affiliation: Department of Neurology, Center for the Study of Neurodegenerative Diseases, University of Virginia, PO Box 800394, Charlottesville, VA 22908, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Thiffault
authors.forename: James P
authors.initials: JP
authors.lastname: Bennett
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D004579:Electron Transport; D006801:Humans; D006822:Hybrid Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; D016572:Cyclosporine; D025261:Mitochondrial Proton-Translocating ATPases