Tight control of mitochondrial membrane potential by cytochrome c oxidase

In the present work we have critically examined the use of the KCN-titration technique in the study of the control of the cellular respiration by cytochrome c oxidase (COX) in the presence of the mitochondrial membrane potential (Delta Psi(mito)) in HepG2 cells. We clearly show that the apparent high inhibition threshold of COX in the presence of maximal Delta psi(mito), is due to the KCN-induced decrease of Delta psi(mito), and not to a low control of COX on the mitochondrial respiration. The tight control exerted by COX on the Delta psi(mito) provides further insights for understanding the pathogenetic mechanisms associated with mitochondrial defects in human neuromuscular degenerative disorders. (C) 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.