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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Silencing Human Cancer: Identification and Uses of MicroRNAs
Recent Patents on Anti-Cancer Drug Discovery Adverse Effects and Drug Interactions of Biologic Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules
Current Medicinal Chemistry Role of Oxygen in Cancer: Looking Beyond Hypoxia
Anti-Cancer Agents in Medicinal Chemistry Positron Emission Tomography Imaging of Tumor Hypoxia
Current Medical Imaging Ubiquitylation and Cancer Development
Current Cancer Drug Targets Editorial [Hot topic: Cell Adhesion Molecules: Structure, Function, Drug Design, and Biomaterials (Executive Editor: Seetharama D. Satyanarayanajois)]
Current Pharmaceutical Design Exploiting EPR in Polymer Drug Conjugate Delivery for Tumor Targeting
Current Pharmaceutical Design Based on Nucleotides Analysis of Tumor Cell Lines to Construct and Validate a Prediction Model of Mechanisms of Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry TRAIL: A Sword for Killing Tumors
Current Medicinal Chemistry Recent Progress in the Development of Anticancer Agents
Current Medicinal Chemistry - Anti-Cancer Agents Meet Our Editorial Board Member
Current Enzyme Inhibition Bioavailability Challenges Associated with Development of Anti-Cancer Phenolics
Mini-Reviews in Medicinal Chemistry Natural Products Targeting Autophagy via the PI3K/Akt/mTOR Pathway as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Molecular Aspects of FKBP51 that Enable Melanoma Dissemination
Current Molecular Pharmacology RNA Interference: A New Targeted Tumour Therapy?
Current Cancer Therapy Reviews Dendritic Cells in Colorectal Cancer and a Potential for their Use in Therapeutic Approaches
Current Pharmaceutical Design Recent Advances in the Use of Metallic Nanoparticles with Antitumoral Action - Review
Current Medicinal Chemistry Cancer Stem-Cells Patents in the Context of their Therapeutic Purposes: Exploring the Latest Trends (2011-2015)
Recent Patents on Regenerative Medicine Designing of Novel Carbonic Anhydrase Inhibitors and Activators
Current Medicinal Chemistry - Cardiovascular & Hematological Agents