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
-
Strategies of Engineering Nanoparticles for Treating Neurodegenerative Disorders
Current Drug Metabolism Versatile Functions of Heat Shock Factors: It is Not All About Stress
Current Immunology Reviews (Discontinued) Effect of Antioxidants on Heavy Metals Induced Conformational Alteration of Cytochrome C and Myoglobin
Protein & Peptide Letters The Proteasome in Health and Disease
Current Pharmaceutical Design The Serum Protein and Lipid Oxidation Marker Levels in Alzheimers Disease and Effects of Cholinesterase Inhibitors and Antipsychotic Drugs Therapy
Current Alzheimer Research L-DOPA and Serotonergic Neurons: Functional Implication and Therapeutic Perspectives in Parkinson's Disease
Central Nervous System Agents in Medicinal Chemistry The Use of Stem Cells in Regenerative Medicine for Parkinson’s and Huntington’s Diseases
Current Medicinal Chemistry Glucose Blood Levels as a Therapeutic Target in Acute Ischaemic Stroke Setting
Current Topics in Medicinal Chemistry Imaging β-Amyloid Plaques and Neurofibrillary Tangles in the Aging Human Brain
Current Pharmaceutical Design Hypoxia as an Initiator of Neuroinflammation: Microglial Connections
Current Neuropharmacology Phenylbutyrate is a Multifaceted Drug that Exerts Neuroprotective Effects and Reverses the Alzheimer´s Disease-like Phenotype of a Commonly Used Mouse Model
Current Pharmaceutical Design Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson’s Disease and Huntington’s Disease: A Review
Current Neuropharmacology Wnt1 Inducible Signaling Pathway Protein 1 (WISP1) Blocks Neurodegeneration through Phosphoinositide 3 Kinase/Akt1 and Apoptotic Mitochondrial Signaling Involving Bad, Bax, Bim, and Bcl-xL
Current Neurovascular Research Meet Our Regional Editor
CNS & Neurological Disorders - Drug Targets BACE1 Structure and Function in Health and Alzheimers Disease
Current Alzheimer Research Protective Effects of Chronic Green Tea Consumption on Age-related Neurodegeneration
Current Pharmaceutical Design Neuroprotective Properties of Standardized Extracts of Hypericum perforatum on Rotenone Model of Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Molecular Docking Study of Catecholamines and [4-(Propan-2-yl) Phenyl]Carbamic acid with Tyrosine Hydroxylase
CNS & Neurological Disorders - Drug Targets Electroencephalography and Dementia: A Literature Review and Future Perspectives
CNS & Neurological Disorders - Drug Targets Diabetic Theory in Anti-Alzheimer’s Drug Research and Development - Part 1: Therapeutic Potential of Antidiabetic Agents
Current Medicinal Chemistry