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 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Neuropharmacology of Cannabinoid System: From Basic Science to Clinical Applications
Current Neuropharmacology Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications
Current Gene Therapy Antioxidants as a Potential Therapy Against Age-Related Neurodegenerative Diseases: Amyloid Beta Toxicity and Alzheimers Disease
Current Pharmaceutical Design Structural and Functional Diversity Among Eukaryotic Hsp70 Nucleotide Exchange Factors
Protein & Peptide Letters An Agathokakological Tale of Δ<sup>9</sup>-THC: Exploration of Possible Biological Targets
Current Drug Targets Hyper-Homocysteinemia Alters Amyloid Peptide-Clusterin Interactions and Neuroglial Network Morphology and Function in the Caudate After Intrastriatal Injection of Amyloid Peptides
Current Alzheimer Research Neurotrophic Effects of the Peptide NAP: A Novel Neuroprotective Drug Candidate
Current Alzheimer Research Peripheral Chemo-Cytokine Profiles in Alzheimers and Parkinsons Diseases
Mini-Reviews in Medicinal Chemistry Alternative Splicing: A Promising Target for Pharmaceutical Inhibition of Pathological Angiogenesis?
Current Pharmaceutical Design Possible Roles of Microglial Cells for Neurotoxicity in Clinical Neurodegenerative Diseases and Experimental Animal Models
Inflammation & Allergy - Drug Targets (Discontinued) Recent Advances in Health Promoting Effect of Dietary Polyphenols
Current Nutrition & Food Science New Therapeutics to Modulate Mitochondrial Function in Neurodegenerative Disorders
Current Pharmaceutical Design Cell Death Targets and Potential Modulators in Alzheimers Disease
Current Pharmaceutical Design Metallothionein I+II Expression as an Early Sign of Chronic Relapsing Experimental Autoimmune Encephalomyelitis in Rats
Current Aging Science Virulence on the Fly: Drosophila melanogaster as a Model Genetic Organism to Decipher Host-Pathogen Interactions
Current Drug Targets Editorial (Thematic Issue: MiRNAcles in the Brain: What to Wish and What to Fear)
CNS & Neurological Disorders - Drug Targets Editorial [Hot Topic: Advances in Alzheimer Therapy: Development of Innovative New Strategies (Guest Editors: Nigel H. Greig, Ezio Giacobini and Debomoy K. Lahiri)]
Current Alzheimer Research Recent Advancements in Liposome-Based Strategies for Effective Drug Delivery to the Brain
Current Medicinal Chemistry Cognitive Decline as a Consequence of Essential Hypertension
Current Pharmaceutical Design Proteomic Approaches Contributing to the Understanding of Neurodegenerative Diseases: Focus on Alzheimers Disease
Current Proteomics