Molecular Mechanisms and Biological Functions of Autophagy for Genetics of Hearing Impairment
Abstract
:1. Introduction
2. The Mechanisms and Biologic Functions of Autophagy
2.1. Autophagy Gene-Dependent Pathways for the Formation of Autophagosome
2.2. Autophagy Regulation by Lysosome through mTORC1 and v-ATPase
3. The Role of Autophagy in Auditory System (or Hearing)
3.1. Otic Epithelium
3.2. Hair Cells, Spiral Ganglion Cells, and Brain Stem Nuclei
3.3. Synapse Ribbon
3.4. Auditory Neurons
4. Autophagy- and Lysosomal-Function-Related Genes and Hearing Loss
4.1. Autophagy-Related Genes Essential for Autophagosome Formation
4.1.1. ATG5 Gene
4.1.2. miRNA 96 Gene
4.2. Lysosomal-Function-Related Genes Essential for the Autophagy–Lysosome Pathway
5. Congenital Disorder of Autophagy with Hearing Loss
β-Propeller Protein-Associated Neurodegeneration (BPAN): Mutations in the WDR45 Gene
6. The Effect of Autophagy for Genetics of Hearing Loss
6.1. Genetics of Sensorineural Hearing Loss (DFNA5 and DFNB59) and Autophagy
6.2. Presbycusis Accelerated by Connexin 26 Partial Loss and Autophagy through Nrf2/Keap1 Pathway
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Gene Locus | Encoding | Genetic Defects | Related Disease | Affected Process of Autophagy |
---|---|---|---|---|---|
Atg5 | 6q21 | ATG protein | Deletion | Autoinflammatory disease Autoimmune disease | Autophagosome formation |
miRNA96 | 7q32.2 | DFNA50 (OMIM #613074) | Point mutations | Sensorineural hearing loss | Autophagosome formation |
WDR45 | Xp11.23 | WD repeat protein | Uncovered mutations | BPAN | Autophagosome formation |
GBA | 1q21 | (Lyso)glucosylceramide | Missense mutations Point mutations Deletions Insertions Splicing aberrations Various rearrangements | Gaucher disease Type 1 (GD1) Type 2 (GD2) Type 3 (GD3) | Lysosome biogenesis |
GLA | Xq22.1 | lysosomal α-galactosidase A | Missense mutations Nonsense mutations Splicing mutations Deletions Insertions | Fabry disease | Lysosome biogenesis |
GAA | 17q25.3 | lysosomal α-glucosidase | Nonsense mutations Multiple exon deletion | Pompe disease | Lysosome biogenesis |
NPC1 | 18q11.2 | NPC protein | Missense mutations Point mutation Duplication mutation Splicing mutation Frame deletion | Niemann–Pick type C | Lysosome biogenesis |
NPC2 | 14q24.3 | NPC protein | Missense mutations of homozygous state | Niemann–Pick type C | Lysosome biogenesis |
IDUA | 4p16.3 | alpha-L-iduronidase | Missense mutations Nonsense mutation Deletion | Mucopolysaccharidoses | Lysosome biogenesis |
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Hayashi, K.; Suzuki, Y.; Fujimoto, C.; Kanzaki, S. Molecular Mechanisms and Biological Functions of Autophagy for Genetics of Hearing Impairment. Genes 2020, 11, 1331. https://doi.org/10.3390/genes11111331
Hayashi K, Suzuki Y, Fujimoto C, Kanzaki S. Molecular Mechanisms and Biological Functions of Autophagy for Genetics of Hearing Impairment. Genes. 2020; 11(11):1331. https://doi.org/10.3390/genes11111331
Chicago/Turabian StyleHayashi, Ken, Yuna Suzuki, Chisato Fujimoto, and Sho Kanzaki. 2020. "Molecular Mechanisms and Biological Functions of Autophagy for Genetics of Hearing Impairment" Genes 11, no. 11: 1331. https://doi.org/10.3390/genes11111331