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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Development of Microfluidic-based Analytical Methodology for Studying the Effects of Chemotherapy Agents on Cancer Tissue
Current Analytical Chemistry CD26/Dipeptidyl Peptidase IV as a Novel Therapeutic Target for Cancer and Immune Disorders
Mini-Reviews in Medicinal Chemistry Angiogenesis Inhibitors: Implications for Combination with Conventional Therapies
Current Pharmaceutical Design Comprehensive Analysis of Key Proteins Involved in Radioresistance of Prostate Cancer by Integrating Protein-protein Interaction Networks
Current Bioinformatics Animal Venoms have Potential to Treat Cancer
Current Topics in Medicinal Chemistry Strategies for Development of Antimalarials Based on Encapsulated Porphyrin Derivatives
Mini-Reviews in Medicinal Chemistry Bortezomib: A New Pro-Apoptotic Agent in Cancer Treatment
Current Cancer Drug Targets Biomarkers of Alzheimer's Disease Risk in Peripheral Tissues; Focus on Buccal Cells
Current Alzheimer Research Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance
Current Neuropharmacology The Role of Culture and Ethnicity in the Adjustment to Gynecological Cancer
Current Women`s Health Reviews Nuclear Magnetic Resonance Spectroscopy of Lipids in Cancer
Current Organic Chemistry HGF-Antagonists: Structure, Activities, and Anti-cancer Approach
Current Signal Transduction Therapy Theranostic Systems and Strategies for Monitoring Nanomedicine-Mediated Drug Targeting
Current Pharmaceutical Biotechnology Interactions of Liposomes with Cells In Vitro and In Vivo: Opsonins and Receptors
Current Drug Metabolism Statins and Type 2 Diabetes Mellitus: An Update After 1 Year
Current Pharmaceutical Design Peniciketal A, A Novel Spiroketal Compound, Exerts Anticancer Effects by Inhibiting Cell Proliferation, Migration and Invasion of A549 Lung Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Vascular Endothelial Growth Factor Receptor 1, a Therapeutic Target in Cancer, Inflammation and Other Disorders
Current Medicinal Chemistry Regulating miRNA by Natural Agents as a New Strategy for Cancer Treatment
Current Drug Targets Targeting mTOR: Evaluating the Therapeutic Potential of Resveratrol for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression
Current Cancer Drug Targets