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.
Keywords: Apoptosis, mitochondria, oligomerization, VDAC1, glycoclysis, oxidative phosphorylation.
Current Medicinal Chemistry
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.
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Cite this article as:
Shoshan-Barmatz Varda*, Krelin Yakov and Chen Quan , VDAC1 as a Player in Mitochondria-Mediated Apoptosis and Target for Modulating Apoptosis, Current Medicinal Chemistry 2017; 24 (40) . https://dx.doi.org/10.2174/0929867324666170616105200
DOI https://dx.doi.org/10.2174/0929867324666170616105200 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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