Cyclical mitochondrial ΔΨM fluctuations linked to electron transport, F0F1 ATP-synthase and mitochondrial Na+/Ca+2 exchange are reduced in Alzheimer's disease cybrids

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 Delta Psi(M) fluctuations ('flickering') in neuroblastoma cells and AD/CTL cybrids. Flickering was blocked by ATP-synthase inhibition, was not observed in rho(0) 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 Delta Psi(M) to F0F1 ATP-synthase; reduction of flickering in AD cybrids suggests dysfunction of this coupling. (c) 2005 Elsevier B.V. and Mitochondria Research Society. All rights reserved.