VDAC activation by the 18 kDa translocator protein

Authors: Leo Veenman Yulia Shandalov Moshe Gavish

Publish Date: 2008/08/01

Volume: 40, Issue: 3, Pages: 199-205

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Abstract

The voltage dependent anion channel VDAC located in the outer mitochondrial membrane functions as a major channel allowing passage of small molecules and ions between the mitochondrial intermembrane space and cytoplasm Together with the adenine nucleotide translocator ANT which is located in the inner mitochondrial membrane the VDAC is considered to form the core of a mitochondrial multiprotein complex named the mitochondrial permeability transition pore MPTP Both VDAC and ANT appear to take part in activation of the mitochondrial apoptosis pathway Other proteins also appear to be associated with the MPTP for example the 18 kDa mitochondrial Translocator Protein TSPO Bcl2 hexokinase cyclophylin D and others Interactions between VDAC and TSPO are considered to play a role in apoptotic cell death As a consequence due to its apoptotic functions the TSPO has become a target for drug development directed to find treatments for neurodegenerative diseases and cancer In this context TSPO appears to be involved in the generation of reactive oxygen species ROS This generation of ROS may provide a link between activation of TSPO and of VDAC to induce activation of the mitochondrial apoptosis pathway ROS are known to be able to release cytochrome c from cardiolipins located at the inner mitochondrial membrane In addition ROS appear to be able to activate VDAC and allow VDAC mediated release of cytochrome c into the cytosol Release of cytochrome c from the mitochondria forms the initiating step for activation of the mitochondrial apoptosis pathway These data provide an understanding regarding the mechanisms whereby VDAC and TSPO may serve as targets to modulate apoptotic rates This has implications for drug design to treat diseases such as neurodegeneration and cancer

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