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
-
Enhancing the Site-Specific Targeting of Macromolecular Anticancer Drug Delivery Systems
Current Drug Targets Bone Morphogenetic Proteins and its Receptors; Therapeutic Targets in Cancer Progression and Bone Metastasis?
Current Pharmaceutical Design The Role of DNA-Microarray in Translational Cancer Research
Current Pharmacogenomics Environmentally Sensitive Paramagnetic and Diamagnetic Contrast Agents for Nuclear Magnetic Resonance Imaging and Spectroscopy
Current Topics in Medicinal Chemistry Targeted Ultrasound Imaging of Cancer: An Emerging Technology on its Way to Clinics
Current Pharmaceutical Design Is Small Really Beautiful? Nanosensors and Low Abundance Biomarkers for Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Aldehyde Dehydrogenase as a Marker for Stem Cells
Current Stem Cell Research & Therapy Engineering Nanomedicines to Overcome Multidrug Resistance in Cancer Therapy
Current Medicinal Chemistry Novel Drugs Targeting Microtubules: the Role of Epothilones
Current Pharmaceutical Design Ceramide-Based Therapeutics for the Treatment of Cancer
Anti-Cancer Agents in Medicinal Chemistry Using Naïve Bayes Algorithm to Estimate the Response to Drug in Lung Cancer Patients
Combinatorial Chemistry & High Throughput Screening Radiolabelled Peptides and Monoclonal Antibodies for Therapy Decision Making in Inflammatory Diseases
Current Pharmaceutical Design MicroRNA-203: Tumor Suppression and Beyond
MicroRNA Interrelationships of Circulating Tumor Cells with Metastasis and Thrombosis: Role of MicroRNAs
Current Pharmaceutical Design Recent Developments in the Chemical Biology of Epothilones
Current Pharmaceutical Design Therapeutic Application of Natural Medicine Monomers in Cancer Treatment
Current Medicinal Chemistry CFTR and MDR: ABC Transporters with Homologous Structure but Divergent Function
Current Genomics Therapeutic Potential of Resveratrol in the Treatment of Glioma: Insights into its Regulatory Mechanisms
Mini-Reviews in Medicinal Chemistry Surface Antigens/Receptors for Targeted Cancer Treatment: The GnRH Receptor / Binding Site for Targeted Adenocarcinoma Therapy
Current Cancer Drug Targets Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy
Current Pharmaceutical Biotechnology