The voltage dependent anion channel affects mitochondrial cholesterol distribution and function.

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.

journal_name

Arch Biochem Biophys

authors

Campbell AM,Chan SH

doi

10.1016/j.abb.2007.06.012

subject

Has Abstract

pub_date

2007-10-15 00:00:00

pages

203-10

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(07)00302-5

journal_volume

466

pub_type

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