Abstract
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the ‘primary LHON mutations’ to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs.
Keywords: mtDNA, LHON, OXPHOS, cybrid, PTP, ROS, ATP, RGCs, Oxidative Stress, Parkinsons Disease, Amyotrophic Lateral Sclerosis, Alzheimer's Disease
Current Genomics
Title: LHON: Mitochondrial Mutations and More
Volume: 12 Issue: 1
Author(s): E. Kirches
Affiliation:
Keywords: mtDNA, LHON, OXPHOS, cybrid, PTP, ROS, ATP, RGCs, Oxidative Stress, Parkinsons Disease, Amyotrophic Lateral Sclerosis, Alzheimer's Disease
Abstract: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the ‘primary LHON mutations’ to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs.
Export Options
About this article
Cite this article as:
Kirches E., LHON: Mitochondrial Mutations and More, Current Genomics 2011; 12 (1) . https://dx.doi.org/10.2174/138920211794520150
DOI https://dx.doi.org/10.2174/138920211794520150 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- 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
-
Anti-cancer Potential of Phyto-alkaloids: A Prospective Review
Current Cancer Therapy Reviews Can Tea Consumption be a Safe and Effective Therapy Against Diabetes Mellitus-Induced Neurodegeneration?
Current Neuropharmacology Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts
Current Cancer Drug Targets Involvement of Cytosolic Phospholipase A2, Calcium Independent Phospholipase A2 and Plasmalogen Selective Phospholipase A2 in Neurodegenerative and Neuropsychiatric Conditions
Current Medicinal Chemistry Dimethyl-Carbamic Acid 2,3-Bis-Dimethylcarbamoyloxy-6-(4-Ethyl-Piperazine- 1-Carbonyl)-Phenyl Ester: A Novel Multi-Target Therapeutic Approach to Neuroprotection
Medicinal Chemistry Implication of Green Tea as a Possible Therapeutic Approach for Parkinson Disease
CNS & Neurological Disorders - Drug Targets Kinases as Targets for Parkinson's Disease: From Genetics to Therapy
CNS & Neurological Disorders - Drug Targets Radiation Therapy Plus Angiogenesis Inhibition with Bevacizumab: Rationale and Initial Experience
Reviews on Recent Clinical Trials Harnessing the Potential of Long Non-coding RNAs to Manage Metabolic Diseases
Current Pharmaceutical Design The Medical Use of Wheatgrass: Review of the Gap Between Basic and Clinical Applications
Mini-Reviews in Medicinal Chemistry Cellular Delivery In Vivo of siRNA-Based Therapeutics
Current Pharmaceutical Design Crosstalk of Long Non-coding RNAs and EMT: Searching the Missing Pieces of an Incomplete Puzzle for Lung Cancer Therapy
Current Cancer Drug Targets The Mitochondriotropic Effects of L-carnitine and its Esters in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Tumor Hypoxia as a Modifier of DNA Strand Break and Cross-Link Repair
Current Molecular Medicine Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Mangiferin – a Bioactive Xanthonoid, not only from Mango and not just Antioxidant
Mini-Reviews in Medicinal Chemistry Biological Evaluation of 8-Hydroxyquinolines as Multi-Target Directed Ligands for Treating Alzheimer’s Disease
Current Alzheimer Research Nucleic Acid Aptamers Against Protein Kinases
Current Medicinal Chemistry Wnt Signaling Pathway in Schizophrenia
CNS & Neurological Disorders - Drug Targets Histopathological Determinants of Tumor Resistance: A Special Look to the Immunohistochemical Expression of Carbonic Anhydrase IX in Human Cancers
Current Medicinal Chemistry