Abstract
Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue.
The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage. While the core autophagic machinery is highly conserved and common to most pathways, the signaling pathways leading to the selective degradation of damaged mitochondria are still not completely understood. Type 1 mitophagy due to nutrient starvation is dependent on PI3K (phosphoinositide 3-kinase) for autophagosome formation but independent of mitophagy proteins, PINK1 (PTEN-induced putative kinase 1) and Parkin. Whereas type 2 mitophagy that occurs due to damage is dependent on PINK1 and Parkin but does not require PI3K.
Autophagy and mitophagy play an important role in human disease and hence could serve as therapeutic targets for the treatment of mitochondrial as well as neurodegenerative disorders. Therefore, we reviewed drugs that are known modulators of autophagy (AICAR and metformin) and may affect this by activating the AMP-activated protein kinase signaling pathways. Furthermore, we reviewed the data available on supplements, such as Coenzyme Q and the quinone idebenone, that we assert rescue increased mitophagy in mitochondrial disease by benefiting mitochondrial function.
Keywords: Mitophagy, AICAR, metformin, Coenzyme Q10, idebenone, phenanthroline.
Current Medicinal Chemistry
Title:Modulating Mitophagy in Mitochondrial Disease
Volume: 25 Issue: 40
Author(s): Eszter Dombi, Heather Mortiboys and Joanna Poulton*
Affiliation:
- Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford,United Kingdom
Keywords: Mitophagy, AICAR, metformin, Coenzyme Q10, idebenone, phenanthroline.
Abstract: Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue.
The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage. While the core autophagic machinery is highly conserved and common to most pathways, the signaling pathways leading to the selective degradation of damaged mitochondria are still not completely understood. Type 1 mitophagy due to nutrient starvation is dependent on PI3K (phosphoinositide 3-kinase) for autophagosome formation but independent of mitophagy proteins, PINK1 (PTEN-induced putative kinase 1) and Parkin. Whereas type 2 mitophagy that occurs due to damage is dependent on PINK1 and Parkin but does not require PI3K.
Autophagy and mitophagy play an important role in human disease and hence could serve as therapeutic targets for the treatment of mitochondrial as well as neurodegenerative disorders. Therefore, we reviewed drugs that are known modulators of autophagy (AICAR and metformin) and may affect this by activating the AMP-activated protein kinase signaling pathways. Furthermore, we reviewed the data available on supplements, such as Coenzyme Q and the quinone idebenone, that we assert rescue increased mitophagy in mitochondrial disease by benefiting mitochondrial function.
Export Options
About this article
Cite this article as:
Dombi Eszter , Mortiboys Heather and Poulton Joanna *, Modulating Mitophagy in Mitochondrial Disease, Current Medicinal Chemistry 2018; 25 (40) . https://dx.doi.org/10.2174/0929867324666170616101741
DOI https://dx.doi.org/10.2174/0929867324666170616101741 |
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
-
Transcriptional Dysregulation in Huntington’s Disease: The Role in Pathogenesis and Potency for Pharmacological Targeting
Current Medicinal Chemistry Structural Determinants of the Multifunctional Profile of Dual Binding Site Acetylcholinesterase Inhibitors as Anti-Alzheimer Agents
Current Pharmaceutical Design Preface [Hot Topic: Transmissible Spongiform Encephalopathies (Prion Diseases) Guest Editors: Xuemin Ye and Richard I. Carp ]
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Resolution-Associated Molecular Patterns (RAMPs) as Endogenous Regulators of Glia Functions in Neuroinflammatory Disease
CNS & Neurological Disorders - Drug Targets New Therapeutic Strategies for Cancer and Neurodegeneration Emerging from Yeast Cell-based Systems
Current Pharmaceutical Design Glutamate Binding-Site Ligands of NMDA Receptors
Current Medicinal Chemistry Heat Shock Proteins Protect Against Ischemia and Inflammation Through Multiple Mechanisms
Inflammation & Allergy - Drug Targets (Discontinued) New Achievements in Bioinformatics Prediction of Post Translational Modification of Proteins
Current Topics in Medicinal Chemistry Role of Neurotrophic Factors in Parkinson's Disease
Current Pharmaceutical Design Histone Deacetylase Inhibitors In Inflammatory Disease
Current Topics in Medicinal Chemistry Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strategies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System
Current Pharmaceutical Design Ectonucleotidases and Nucleotide/Nucleoside Transporters as Pharmacological Targets for Neurological Disorders
CNS & Neurological Disorders - Drug Targets Possible Neuroprotective Strategies for Huntingtons Disease
Current Neuropharmacology Radiolabeled Peptides for Alzheimer’s Diagnostic Imaging: Mini Review
Current Radiopharmaceuticals Pharmacological Properties and Therapeutic Potential of Naringenin: A Citrus Flavonoid of Pharmaceutical Promise
Current Pharmaceutical Design The Role of α7 Nicotinic Acetylcholine Receptors and α7-Specific Antibodies in Neuroinflammation Related to Alzheimer Disease
Current Pharmaceutical Design Preface:
CNS & Neurological Disorders - Drug Targets The Role of Neurogenesis in Neurodegenerative Diseases and its Implications for Therapeutic Development
CNS & Neurological Disorders - Drug Targets Omega-3 Fatty Acids as Druggable Therapeutics for Neurodegenerative Disorders
CNS & Neurological Disorders - Drug Targets Hematopoietic Stem Cells Therapies
Current Stem Cell Research & Therapy