Abstract
Mitochondria play a crucial role in multitude of cellular processes including energy production, calcium signaling, and apoptosis. This remarkable organelle constantly undergoes a complex cycle of fusion and fission, a crucial quality control system for maintaining homeostasis of the cell. Any impairment in this dynamic behavior is linked to a wide range of cellular abnormalities. Consistent with this concept, neuronal apoptosis often emanates in conjunction with rampant mitochondrial fragmentation. The mitochondrial dynamics are tightly regulated by a master mediator called Dynamin related protein 1 (Drp1), which in normal conditions facilitates mitochondrial fission. However, diverse stress conditions induce intensified translocation of cytosolic Drp1 to the mitochondria, contributing excessive fragmentation and concomitant apoptosis. Despite this knowledge, crucial questions such as how fission of the inner and outer mitochondrial membranes is coordinated and how these processes are linked to apoptosis and necrosis remain to be answered. This review focuses on delineating the mechanism of Drp1 activation and explores the pathophysiological importance of dysregulated mitochondrial fission with a special emphasis on ischemic stroke. Further, it also provides a new mechanistic link between ischemia and Drp1-mediated mitochondrial fission.
Keywords: Cerebral ischemia, mitochondrial fission, dynamin related protein 1, apoptosis.
Current Medicinal Chemistry
Title:Drp1 in Ischemic Neuronal Death: An Unusual Suspect
Volume: 21 Issue: 19
Author(s): H. Pradeep, B. Sharma and G.K. Rajanikant
Affiliation:
Keywords: Cerebral ischemia, mitochondrial fission, dynamin related protein 1, apoptosis.
Abstract: Mitochondria play a crucial role in multitude of cellular processes including energy production, calcium signaling, and apoptosis. This remarkable organelle constantly undergoes a complex cycle of fusion and fission, a crucial quality control system for maintaining homeostasis of the cell. Any impairment in this dynamic behavior is linked to a wide range of cellular abnormalities. Consistent with this concept, neuronal apoptosis often emanates in conjunction with rampant mitochondrial fragmentation. The mitochondrial dynamics are tightly regulated by a master mediator called Dynamin related protein 1 (Drp1), which in normal conditions facilitates mitochondrial fission. However, diverse stress conditions induce intensified translocation of cytosolic Drp1 to the mitochondria, contributing excessive fragmentation and concomitant apoptosis. Despite this knowledge, crucial questions such as how fission of the inner and outer mitochondrial membranes is coordinated and how these processes are linked to apoptosis and necrosis remain to be answered. This review focuses on delineating the mechanism of Drp1 activation and explores the pathophysiological importance of dysregulated mitochondrial fission with a special emphasis on ischemic stroke. Further, it also provides a new mechanistic link between ischemia and Drp1-mediated mitochondrial fission.
Export Options
About this article
Cite this article as:
Pradeep H., Sharma B. and Rajanikant G.K., Drp1 in Ischemic Neuronal Death: An Unusual Suspect, Current Medicinal Chemistry 2014; 21 (19) . https://dx.doi.org/10.2174/0929867321666131228203513
DOI https://dx.doi.org/10.2174/0929867321666131228203513 |
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
-
MicroRNAs: An Apparent Switch for High-Altitude Pulmonary Edema
MicroRNA Bladder Cancer: Update on Risk Factors, Molecular and Ultrastructural Patterns
Current Medicinal Chemistry Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery
Current Drug Targets Design, Synthesis and Biological Screening of Some Pyridinylpyrazole and Pyridinylisoxazole Derivatives as Potential Anti-inflammatory, Analgesic, Antipyretic and Antimicrobial Agents
Medicinal Chemistry Tachykinins and their Receptors in Human Malignancies
Current Drug Targets Drug Delivery Systems for Brain Tumor Therapy
Current Pharmaceutical Design Tumor Dormancy and the Angiogenic Switch: Possible Implications of Bone Marrow- Derived Cells
Current Pharmaceutical Design Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment
Current Cancer Drug Targets Fusogenic Oncolytic Herpes Simplex Viruses as a Potent and Personalized Cancer Vaccine
Current Pharmaceutical Biotechnology Suppression of NF-κB Signaling and P-glycoprotein Function by Gambogic Acid Synergistically Potentiates Adriamycin -induced Apoptosis in Lung Cancer
Current Cancer Drug Targets Anti-diabetic Drug Metformin: Challenges and Perspectives for Cancer Therapy
Current Cancer Drug Targets Emergence of Nanomedicine as Cancer Targeted Magic Bullets: Recent Development and Need to Address the Toxicity Apprehension
Current Drug Discovery Technologies Antitumour Activity of Muricatacin Isomers and its Derivatives in Human Colorectal Carcinoma Cell HCT116
Anti-Cancer Agents in Medicinal Chemistry A Systems Medicine Clinical Platform for Understanding and Managing Non- Communicable Diseases
Current Pharmaceutical Design Cardiovascular Effects of EGFR (Epidermal Growth Factor Receptor) Monoclonal Antibodies
Cardiovascular & Hematological Agents in Medicinal Chemistry Apoptosis Imaging to Monitor Cancer Therapy: The Road to Fast Treatment Evaluation?
Current Pharmaceutical Biotechnology MiRNA-based Therapeutics for Lung Cancer
Current Pharmaceutical Design Liposomes as Versatile Platform for Cancer Theranostics: Therapy, Bio-imaging, and Toxicological Aspects
Current Pharmaceutical Design Study of Intercellular Adhesion Molecule-1 (ICAM-1) in Bone Homeostasis
Current Drug Targets The Chlorophyll Catabolite Pheophorbide a as a Photosensitizer for the Photodynamic Therapy
Current Medicinal Chemistry