Abstract
Hexokinase II is often highly expressed in poorly differentiated and rapidly growing tumors that exhibit a high rate of aerobic glycolysis. Hexokinase II binds to the mitochondrial membrane through its interaction with the outer membrane voltage-dependent anion channel (VDAC), preferentially at contact sites between the outer and inner mitochondrial membrane. This location is thought to be important for the integration of glycolysis with mitochondrial energy metabolism. VDAC is a critical component of the mitochondrial phase of apoptosis and its interaction with Bcl-2 family proteins controls the rate of release of mitochondrial intermembrane space proteins that activate the execution phase of apoptosis. The proteins involved in the contact sites also constitute the mitochondrial permeability transition, one of the mechanisms by which mitochondrial protein release can be mediated. Hexokinase II binding to VDAC suppresses the release of intermembrane space proteins and inhibits apoptosis, thereby contributing to the survival advantage of tumor cells. This interaction places hexokinase II in a position to integrate glycolytic metabolism of the tumor cell with the control of apoptosis at the mitochondrial level. Mitochondrial binding of hexokinase II may constitute an attractive target for therapeutic intervention to suppress tumor growth.
Keywords: hexokinase II, energy metabolism, membrane voltage-dependent anion channel, vdac, apoptosis control
Current Medicinal Chemistry
Title: Hexokinase II: The Integration of Energy Metabolism and Control of Apoptosis
Volume: 10 Issue: 16
Author(s): John G. Pastorino and Jan B. Hoek
Affiliation:
Keywords: hexokinase II, energy metabolism, membrane voltage-dependent anion channel, vdac, apoptosis control
Abstract: Hexokinase II is often highly expressed in poorly differentiated and rapidly growing tumors that exhibit a high rate of aerobic glycolysis. Hexokinase II binds to the mitochondrial membrane through its interaction with the outer membrane voltage-dependent anion channel (VDAC), preferentially at contact sites between the outer and inner mitochondrial membrane. This location is thought to be important for the integration of glycolysis with mitochondrial energy metabolism. VDAC is a critical component of the mitochondrial phase of apoptosis and its interaction with Bcl-2 family proteins controls the rate of release of mitochondrial intermembrane space proteins that activate the execution phase of apoptosis. The proteins involved in the contact sites also constitute the mitochondrial permeability transition, one of the mechanisms by which mitochondrial protein release can be mediated. Hexokinase II binding to VDAC suppresses the release of intermembrane space proteins and inhibits apoptosis, thereby contributing to the survival advantage of tumor cells. This interaction places hexokinase II in a position to integrate glycolytic metabolism of the tumor cell with the control of apoptosis at the mitochondrial level. Mitochondrial binding of hexokinase II may constitute an attractive target for therapeutic intervention to suppress tumor growth.
Export Options
About this article
Cite this article as:
Pastorino G. John and Hoek B. Jan, Hexokinase II: The Integration of Energy Metabolism and Control of Apoptosis, Current Medicinal Chemistry 2003; 10 (16) . https://dx.doi.org/10.2174/0929867033457269
DOI https://dx.doi.org/10.2174/0929867033457269 |
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
- Bentham Author Support Services (BASS)
- 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
-
Essential Role of Gli Proteins in Glioblastoma Multiforme
Current Protein & Peptide Science Is the Epithelial-to-Mesenchymal Transition Clinically Relevant for the Cancer Patient?
Current Pharmaceutical Biotechnology Chemoprevention Gene Therapy (CGT) of Pancreatic Cancer Using Perillyl Alcohol and a Novel Chimeric Serotype Cancer Terminator Virus
Current Molecular Medicine Angiotensin Peptides and Lung Cancer
Current Cancer Drug Targets Safety and Utilization of Blood Components as Therapeutic Delivery Systems
Current Pharmaceutical Biotechnology Synthesis of Arylpiperazine Derivatives as Protease Activated Receptor 1 Antagonists and Their Evaluation as Antiproliferative Agents
Anti-Cancer Agents in Medicinal Chemistry Gold Nanoparticle-Based Drug Delivery Platform for Antineoplastic Chemotherapy
Current Drug Metabolism Determinants of Anti-Cancer Effect of Mitochondrial Electron Transport Chain Inhibitors: Bioenergetic Profile and Metabolic Flexibility of Cancer Cells
Current Pharmaceutical Design Manipulation of Glycolysis in Malignant Tumors: Fantasy or Therapy?
Current Medicinal Chemistry One Hundred Faces of Cyclopamine
Current Pharmaceutical Design Role of Cardiolipin in Mitochondrial Diseases and Apoptosis
Current Medicinal Chemistry Responsive Role of Nanomedicine in the Tumor Microenvironment and Cancer Drug Resistance
Current Medicinal Chemistry Cell Cycle and Energy Metabolism in Tumor Cells: Strategies for Drug Therapy
Recent Patents on Anti-Cancer Drug Discovery Brain Tumor Detection and Classification by Hybrid CNN-DWA Model Using MR Images
Current Medical Imaging In Vivo Anticancer Activity, Toxicology and Histopathological Studies of the Thiolate Gold(I) Complex [Au(Spyrimidine)(PTA-CH<sub>2</sub>Ph)]Br
Anti-Cancer Agents in Medicinal Chemistry Synthetic and Biological Vesicular Nano-Carriers Designed for Gene Delivery
Current Pharmaceutical Design Impediment of Cancer by Dietary Plant-derived Alkaloids Through Oxidative Stress: Implications of PI3K/AKT Pathway in Apoptosis, Autophagy, and Ferroptosis
Current Topics in Medicinal Chemistry Arylpyrazoles: Heterocyclic Scaffold of Immense Therapeutic Application
Current Organic Chemistry Recent Advances in the Development of 14-Alkoxy Substituted Morphinans as Potent and Safer Opioid Analgesics
Current Medicinal Chemistry Secondary Hypertension: The Ways of Management
Current Vascular Pharmacology