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
-
Harnessing the Natural Pool of Polyketide and Non-ribosomal Peptide
Family: A Route Map towards Novel Drug Development
Current Molecular Pharmacology Circulating Levels of Soluble Angiogenic Factors in Multiple Myeloma: Correlation with Parameters of Disease Activity and Prognosis
Current Angiogenesis (Discontinued) The Brain Protective Effect of rTMS (Repetitive Transcranial Magnetic Stimulation) in Depression: A Mini-Review in Animal Studies
Medicinal Chemistry Cytotoxic and Allergenic Potential of Bioactive Proteins and Peptides
Current Pharmaceutical Design Cyclodepsipeptides - Potential Drugs and Lead Compounds in the Drug Development Process
Current Medicinal Chemistry Apoptosis-Inducing Activity of the S100A8/A9 Heterodimer
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry MicroRNAs: Potential Diagnostic and Therapeutic Targets for Breast Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases
Current Drug Targets New Use for Old Drugs? Prospective Targets of Chloroquines in Cancer Therapy
Current Drug Targets Monoamine Oxidase Inhibition and Molecular Modeling Studies of Piperidyl-thienyl and 2-Pyrazoline Derivatives of Chalcones
Medicinal Chemistry Fatty Acid Synthase: A Target for the Reversal of Liver Steatosis
Current Enzyme Inhibition Advances in Pyrazole Based Scaffold as Cyclin-dependent Kinase 2 Inhibitors for the Treatment of Cancer
Mini-Reviews in Medicinal Chemistry Selective Inhibitors of Histone Deacetylase 10 (HDAC-10)
Current Medicinal Chemistry Processing of Amyloid Precursor Protein and Amyloid Peptide Neurotoxicity
Current Alzheimer Research Grape Seed Proanthocyanidins Protect N2a Cells against Ischemic Injury via Endoplasmic Reticulum Stress and Mitochondrial-associated Pathways
CNS & Neurological Disorders - Drug Targets Nutritional Aspects Relating to the Developmental Origins of Health and Disease
Current Women`s Health Reviews T Cell Suicide Gene Therapy to Aid Haematopoietic Stem Cell Transplantation
Current Gene Therapy The MYC Oncogene as a Cancer Drug Target
Current Cancer Drug Targets Lipid Nanoparticles as Vehicles for Macromolecules: Nucleic Acids and Peptides
Recent Patents on Drug Delivery & Formulation Edelfosine in Membrane Environment - the Langmuir Monolayer Studies
Anti-Cancer Agents in Medicinal Chemistry