The Role of Lipids in VDAC Oligomerization

Evidence has accumulated that the voltage-dependent anion channel (VDAC), located on the outer membrane of mitochondria, plays a central role in apoptosis. The involvement of VDAC oligomerization in apoptosis has been suggested in various studies. However, it still remains unknown how exactly VDAC s...

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Bibliographic Details
Published in:Biophysical journal 2012-02, Vol.102 (3), p.523-531
Main Authors: Betaneli, Viktoria, Petrov, Eugene P., Schwille, Petra
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cardiolipins - metabolism
Cattle
Cell Membrane - chemistry
Cell Membrane - metabolism
Detergents - chemistry
fluorescence
Humans
lipid composition
lipids
Membrane
metabolism
mitochondria
Mitochondria - metabolism
mitochondrial membrane
Models, Molecular
Phosphatidylglycerols - metabolism
Phospholipids - metabolism
Protein Multimerization
Protein Structure, Quaternary
Spectrometry, Fluorescence
spectroscopy
Unilamellar Liposomes - chemistry
Unilamellar Liposomes - metabolism
Voltage-Dependent Anion Channel 1 - chemistry
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Summary:Evidence has accumulated that the voltage-dependent anion channel (VDAC), located on the outer membrane of mitochondria, plays a central role in apoptosis. The involvement of VDAC oligomerization in apoptosis has been suggested in various studies. However, it still remains unknown how exactly VDAC supramolecular assembly can be regulated in the membrane. This study addresses the role of lipids in this process. We investigate the effect of cardiolipin (CL) and phosphatidylglycerol (PG), anionic lipids important for mitochondria metabolism and apoptosis, on VDAC oligomerization. By applying fluorescence cross-correlation spectroscopy to VDAC reconstituted into giant unilamellar vesicles, we demonstrate that PG significantly enhances VDAC oligomerization in the membrane, whereas cardiolipin disrupts VDAC supramolecular assemblies. During apoptosis, the level of PG in mitochondria increases, whereas the CL level decreases. We suggest that the specific lipid composition of the outer mitochondrial membrane might be of crucial relevance and, thus, a potential cue for regulating the oligomeric state of VDAC.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2011.12.049