Age-related macular degeneration (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none BoldLegendmTORC1AMPKRetinal pigmentepithelial cellIndirect regulationMalateMitochondrionorganizationand biogenesisSIRT1MTORRPTORMLST8RPS6KB1MAPK3PMAIP1MDH1AlphaPRKAA1PRKAA2PRKAB1PRKAB2PRKAG1PRKAG2PRKAG3BetaGammaLipiddegenerationAutophagyRibosomebiogenesis andassemblyGlycolysisMitochondrialdamageApoptosisOxaloacetateNAD+PARP2PPARGC1ANucleusRPTORDirect regulationExpression regulationProtein modificationor bindingItalicUpregulated in AMD vs. normalDownregulated in AMD vs. normalName: Age-related macular degenerationOrganism: Homo sapiens


Description

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)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7016007/).

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Bibliography

  1. Zhang M, Jiang N, Chu Y, Postnikova O, Varghese R, Horvath A, Cheema AK, Golestaneh N; ''Dysregulated metabolic pathways in age-related macular degeneration.''; Sci Rep, 2020 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
138229view01:21, 26 March 2025EweitzFix truncated text
138219view12:23, 25 March 2025EweitzConvey up- vs. down-regulation in disease via font style, refine legend
138218view12:03, 25 March 2025EweitzRefine interactions, start legend
138217view03:59, 25 March 2025EweitzOntology Term : 'age related macular degeneration' added !
138216view03:59, 25 March 2025EweitzOntology Term : 'retinal pigment epithelial cell' added !
138215view03:59, 25 March 2025EweitzModified description
138214view03:57, 25 March 2025EweitzModified description
138213view03:56, 25 March 2025EweitzModified description
138212view03:51, 25 March 2025EweitzAdd literature reference
138211view03:49, 25 March 2025EweitzLabel cell type
138210view03:42, 25 March 2025EweitzAdd more interactions
138209view03:31, 25 March 2025EweitzConvert unknowns to pathways, add cell compartments
138208view03:20, 25 March 2025EweitzUpgrade nodes, identify pathways
138207view03:15, 25 March 2025EweitzIdentify metabolites
138206view02:56, 25 March 2025EweitzEconomize layout
138205view02:53, 25 March 2025EweitzAdd interactions
138204view02:25, 25 March 2025EweitzAdd process, metabolite nodes
138203view02:09, 25 March 2025EweitzArrange nodes
138202view21:46, 24 March 2025EweitzAdd AMPK complex, with explicit genes
138201view21:44, 24 March 2025EweitzNew pathway

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
ApoptosisPathwayWP254 (WikiPathways)
AutophagyPathwayWP4923 (WikiPathways)
GlycolysisPathwayWP534 (WikiPathways)
Lipid degenerationPathway
MAPK3GeneProductENSG00000102882 (Ensembl)
MDH1GeneProductENSG00000014641 (Ensembl)
MLST8GeneProductENSG00000167965 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MalateMetaboliteCHEBI:25115 (ChEBI)
Mitochondrial damagePathway
Mitochondrion

organization

and biogenesis
Pathway
NAD+MetaboliteCHEBI:15846 (ChEBI)
OxaloacetateMetaboliteCHEBI:16452 (ChEBI)
PARP2GeneProductENSG00000129484 (Ensembl)
PMAIP1GeneProductENSG00000141682 (Ensembl)
PPARGC1AGeneProductENSG00000109819 (Ensembl) "PGC1a" in source
PRKAA1GeneProductENSG00000132356 (Ensembl)
PRKAA2GeneProductENSG00000162409 (Ensembl)
PRKAB1GeneProductENSG00000111725 (Ensembl)
PRKAB2GeneProductENSG00000131791 (Ensembl)
PRKAG1GeneProductENSG00000181929 (Ensembl)
PRKAG2GeneProductENSG00000106617 (Ensembl)
PRKAG3GeneProductENSG00000115592 (Ensembl)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RPTORGeneProductENSG00000141564 (Ensembl)
Ribosome

biogenesis and

assembly
Pathway
SIRT1GeneProductENSG00000096717 (Ensembl)

Annotated Interactions

No annotated interactions

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