Title:VDAC1 as a Player in Mitochondria-Mediated Apoptosis and Target for Modulating Apoptosis
Volume: 24
Issue: 40
Author(s): Varda Shoshan-Barmatz*, Yakov Krelin and Quan Chen
Affiliation:
- Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105,Israel
Keywords:
Apoptosis, mitochondria, oligomerization, VDAC1, glycoclysis, oxidative phosphorylation.
Abstract: Background: The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria
membrane protein, functions as a mitochondrial governor, controlling transport of
metabolites in and out of the mitochondria and energy production, while also coordinating
glycolysis and oxidative phosphorylation. VDAC1 plays a key role in mitochondria-mediated
apoptosis by functioning in the release of apoptotic proteins located in the inter-membranal
space and due to its association with pro- and anti-apoptotic proteins. Thus, VDAC1 is considered
as a promising target for controlling apoptosis.
Methods: We reviewed published data presenting accumulated evidence suggesting that
VDAC1 oligomerization represents an important step in the intrinsic mitochondria-mediated
apoptosis pathway.
Results: The published data support the proposal that VDAC1 oligomerization leads to the
formation of a large pore that allows the release of pro-apoptotic proteins to the cytosol,
thereby, activation of apoptosis. Evidence for the relationship between VDAC1 expression
levels and induction of apoptosis are presented. This includes the finding that almost all apoptosis
stimuli induce VDAC1 over-expression shifting VDAC1 from a monomeric to an oligomeric
assembly, corresponding to the Cyto c release channel. Copounds or conditions inducing
VDAC1 over-expression, VDAC1 oligomerization and apoptosis are presented. Likewise,
VDAC1-interacting molecules, that inhibit both VDAC1 oligomerization and apoptosis
are also presented.
Conclusion: This review highlights the findings about VDAC1 oligomerization as a potential
target for controlling apoptosis, specifically using drugs to induce apoptotic cell death in cancer
and inhibit apoptosis in neurodegenerative diseases, as well as possible VDAC1-based
therapeutic applications.
