Channelpedia

PubMed 21033348


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv10.1



Title: [The role of the voltage-dependent anion channels in the outer membrane of mitochondria in the regulation of cellular metabolism].

Authors: E L Kholmukhamedov, C Czerny, G Lovelace, K C Beeson, T Baker, C B Johnson, P Pediaditakis, V V Teplova, A Tikunov, J MacDonald, J J Lemasters

Journal, date & volume: Biofizika, 2010 Sep-Oct , 55, 822-33

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21033348


Abstract
The role of the voltage-dependent anion channels (VDAC) harbored in the outer membrane of mitochondria in the regulation of cellular metabolism was investigated using an experimental model of ethanol toxicity in cultured hepatocytes. It was demonstrated that ethanol inhibits State 3 and uncoupled mitochondrial respirations, decreases the accessibility of mitochondrial adenylate kinase localized in the intermembrane space of mitochondria, and suppresses ureagenic respiration and synthesis of urea in cultured hepatocytes. Increasing the permeability of the outer mitochondrial membrane with closed VDAC with high concentrations of digitonin (> 80 microM), which creates pores in the membrane, allowing the alternative bypass of closed VDAC, and restores all reactions suppressed with ethanol. It is concluded that the effect of ethanol in hepatocytes leads to global loss of mitochondrial functions due to the closure of VDAC, which limits the free diffusion of metabolites into the intermembrane space of mitochondria. Our studies demonstrated that ethanol affects the main mitochondrial functions and revealed the role of VDAC channels in the outer mitochondrial membrane in the regulation of liver specific intracellular processes such as ureagenesis. The data obtained can be used for the development of pharmaceutical drugs that prevent the closure of VDAC in mitochondria of ethanol oxidizing liver, thus protecting liver tissue from the hepatotoxic action of alcohol.