Age-related macular degeneration (WP5526)
Homo sapiens
Age-related macular degeneration (AMD) is a leading cause of vision impairment in individuals aged 55 and older in the Western world. This diagram shows metabolic pathway crosstalk in AMD. In AMD, the upregulation of PARP2 expression leads to the downregulation of SIRT1. The depletion of SIRT1, a NAD+-dependent deacetylase, causes acetylation and inactivation of PGC-1α. Reduced SIRT1 levels activate the TORC1 complex in AMD, which inhibits autophagy through phosphorylation-mediated suppression of Atg13 and ULK1. Additionally, activated mTOR enhances glycolysis. MAPK3 expression is reduced in AMD RPE cells, which can result in increased PMAIP1 mRNA levels, leading to higher NOXA protein expression. NOXA promotes changes in the mitochondrial membrane and the release of apoptogenic proteins. MDH1, a key gene in energy metabolism, is upregulated in AMD RPE cells. This cytosolic enzyme plays an essential role in the malate-aspartate shuttle, allowing malate to pass through the mitochondrial membrane, and facilitates the NAD/NADH-dependent reversible oxidation of oxaloacetate to malate. In AMD RPE cells, reduced AMPK activity may disrupt both catabolic and anabolic processes, further downregulating PGC-1α and SIRT1. Inspired by Figure 7 in Zhang et al. (2020).
Authors
Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Annotations
Disease Ontology
age related macular degenerationCell Type Ontology
retinal pigment epithelial cellLabel | Type | Compact URI | Comment |
---|---|---|---|
Malate | Metabolite | chebi:25115 | |
Oxaloacetate | Metabolite | chebi:16452 | |
NAD+ | Metabolite | chebi:15846 | |
SIRT1 | GeneProduct | ensembl:ENSG00000096717 | |
MTOR | GeneProduct | ensembl:ENSG00000198793 | |
RPS6KB1 | GeneProduct | ensembl:ENSG00000108443 | |
MAPK3 | GeneProduct | ensembl:ENSG00000102882 | |
PMAIP1 | GeneProduct | ensembl:ENSG00000141682 | |
MDH1 | GeneProduct | ensembl:ENSG00000014641 | |
RPTOR | GeneProduct | ensembl:ENSG00000141564 | |
MLST8 | GeneProduct | ensembl:ENSG00000167965 | |
PRKAA1 | GeneProduct | ensembl:ENSG00000132356 | |
PRKAA2 | GeneProduct | ensembl:ENSG00000162409 | |
PRKAB1 | GeneProduct | ensembl:ENSG00000111725 | |
PRKAB2 | GeneProduct | ensembl:ENSG00000131791 | |
PRKAG1 | GeneProduct | ensembl:ENSG00000181929 | |
PRKAG2 | GeneProduct | ensembl:ENSG00000106617 | |
PRKAG3 | GeneProduct | ensembl:ENSG00000115592 | |
PARP2 | GeneProduct | ensembl:ENSG00000129484 | |
PPARGC1A | GeneProduct | ensembl:ENSG00000109819 | 'PGC1a' in source |
References
- Dysregulated metabolic pathways in age-related macular degeneration. Zhang M, Jiang N, Chu Y, Postnikova O, Varghese R, Horvath A, et al. Sci Rep. 2020 Feb 12;10(1):2464. PubMed Europe PMC Scholia