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 Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Disease Ontology

age related macular degeneration

Cell Type Ontology

retinal pigment epithelial cell

Participants

Label 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

  1. 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