Abstract
Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Mitophagy, a mitochondria-specific type of autophagy, is an essential part of mitochondrial quality control, the collective mechanism responsible for this organelle’s homeostasis. The abundance of ROS, DNA damage, and the excessive energy consumption in the ageing retina all contribute to the degeneration of RPE cells and their mitochondria. We discuss the role of mitophagy in the cell and argue that its impairment may play a role in AMD pathogenesis. Thus, mitophagy as a potential therapeutic target in AMD and other degenerative diseases is as well explored.
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Abbreviations
- AMBRA1:
-
Activating molecule in beclin-1-regulated autophagy
- AMD:
-
Age-related macular degeneration
- AMPK:
-
AMP-activated protein kinase
- ARE:
-
Antioxidant-binding element
- Atg:
-
Autophagy-related gene
- DMT1:
-
Divalent metal transporter 1
- ER:
-
Endoplasmic reticulum
- FPN1:
-
Ferroportin 1
- FPF:
-
Flavoprotein fluorescence
- FtMt:
-
Mitochondrial ferritin
- Gp78:
-
Glycoprotein 78
- HDAC6:
-
Histone deacetylase 6
- HIF-1α:
-
Hypoxia-inducible factor-1α
- Hsp:
-
Heat-shock protein
- IMM:
-
Inner mitochondrial membrane
- Keap1:
-
Kelch-like ECH-associated protein 1
- LIR:
-
MAPK1LC3-interacting region
- MAM:
-
Mitochondria-associated endoplasmic reticulum membrane
- MAPK:
-
Mitogen-activated protein kinase
- MAPK1LC3:
-
Microtubule-associated protein 1 light-chain 3
- Mfn:
-
Mitofusin
- MMP:
-
Mitochondrial membrane potential
- MPT:
-
Mitochondrial permeability transition
- MRC:
-
Mitochondrial respiratory chain
- mtDNA:
-
Mitochondrial DNA
- mTORC1:
-
Mammalian target of rapamycin complex 1
- Mul1:
-
Mitochondrial E3 ubiquitin ligase
- Nrf2:
-
Nuclear factor (erythroid-derived 2)-related factor 2
- OMM:
-
Outer mitochondrial membrane
- PGC-1α:
-
Peroxisome proliferator-activated receptor gamma coactivator-1α
- PI3K:
-
Phosphatidylinosotole-3-kinase
- PINK1:
-
Phosphatase and tensin homologue-induced putative kinase
- POS:
-
Photoreceptor outer segment
- ROS:
-
Reactive oxygen species
- RGC:
-
Retinal ganglion cell
- RPE:
-
Retinal pigment epithelium
- SAMD:
-
Senescence-associated mitochondrial dysfunction
- SASP:
-
Senescent-associated secretory phenotype
- Sirt1:
-
NAD-dependent deacetylase Sirtuin 1
- Smurf1:
-
SMAD-specific E3 ubiquitin protein ligase 1
- SOD:
-
Superoxide dismutase
- SQSTM1/p62:
-
Sequestosome1/p62
- Tfam:
-
Mitochondrial transcription factor A
- TIM:
-
Translocase of the inner mitochondrial membrane
- TOM:
-
Translocase of the outer mitochondrial membrane
- Ub:
-
Ubiquitin
- VDAC:
-
Voltage-dependent anion channel
- VEGF:
-
Vascular endothelial growth factor
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The authors thank Mr. Thomas Dunlop for checking the language of the manuscript.
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Hyttinen, J.M.T., Viiri, J., Kaarniranta, K. et al. Mitochondrial quality control in AMD: does mitophagy play a pivotal role?. Cell. Mol. Life Sci. 75, 2991–3008 (2018). https://doi.org/10.1007/s00018-018-2843-7
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DOI: https://doi.org/10.1007/s00018-018-2843-7