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Mitochondrial membrane cholesterol and the effect on cellular energy production
Author(s) -
Campbell Andrew Mark,
Chan Samuel H.P.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb45-a
Subject(s) - voltage dependent anion channel , mitochondrion , oxidative phosphorylation , inner mitochondrial membrane , atp–adp translocase , microbiology and biotechnology , biochemistry , cholesterol , chemistry , adenosine triphosphate , adenine nucleotide translocator , translocase , phosphorylation , translocase of the inner membrane , biology , mitochondrial membrane transport protein , bacterial outer membrane , chromosomal translocation , escherichia coli , gene
The optimal function of many important mitochondrial enzymes is dependent on membrane cholesterol content and membrane fluidity. Data show that the cholesterol level of the mitochondrial membranes greatly affects the activity of the membrane associated proteins involved in oxidative phosphorylation, such as the adenine nucleotide translocase (ANT). We have observed abnormally high membrane cholesterol levels in mitochondria from cultured MH‐7777 hepatoma cells and that these cells exhibit deficient ATP/ADP exchange along with a related decrease in energy production via oxidative phosphorylation. Using cholesterol affinity chromatography and MALDI‐TOF mass spectrometry, we have identified the voltage dependent anion channel (VDAC) as a component of a complex protein dependent mechanism that is involved in the transportation of cholesterol and maintenance of proper mitochondrial membrane cholesterol ratios. In addition, preliminary results indicate a role for this protein complex in the failure of cholesterol elevated mitochondria from hepatoma cells to exhibit atractyloside induced mitochondrial permeability transition pore (MPT) formation, a potential precursor of apoptosis. We report here the method of a protein dependent mechanism involving the protein VDAC to regulate membrane cholesterol content as well as the subsequent effect on mitochondrial energetic productivity and normal function. This research was supported by the National Institute of Health Grant CA‐20454.