The voltage dependent anion channel affects mitochondrial cholesterol distribution and function

Andrew M. Campbell, Samuel H.P. Chan

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

We have observed abnormally high membrane cholesterol levels and a subsequent deficiency of oxidative energy production in mitochondria from cultured Morris hepatoma cells (MH7777). Using cholesterol affinity chromatography and MALDI-TOF Mass Spectrometry, we have identified the voltage dependent anion channel (VDAC) as a necessary component of a protein complex involved in mitochondrial membrane cholesterol distribution. VDAC is known to associate strongly with hexokinase, particularly in glycolytic cancers. By constructing an E72Q mutant form of VDAC that inhibits its binding of hexokinase, we report an increase in oxidative phosphorylation activity of MH7777 cells, as well as reduced membrane cholesterol ratios to levels near that of normal liver mitochondria. This paper demonstrates that the ability of VDAC to influence mitochondrial membrane cholesterol distribution may have implications on mitochondrial characteristics such as oxidative phosphorylation and induction of apoptosis, as well as the propensity of cancer cells to exhibit a glycolytic phenotype.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume466
Issue number2
DOIs
StatePublished - Oct 15 2007

Keywords

  • Cholesterol transport
  • Contact sites
  • Mitochondria
  • Oxidative phosphorylation
  • Voltage dependent anion channel
  • Warburg effect

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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