NAD metabolism in oncogene-induced senescence and mitochondrial dysfunction-associated senescence (Homo sapiens)

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3, 75875872757585787658755555551, 5684, 95MITOCHONDRIAMitochondrial Dysfunction-Associated SenescenceCell SenescenceCYTOPLASMGrowth ArrestCommon forboth pathwaysPentose PhospatePathwayPromotion ofCancer ProgressionPARP1nicotinamideSA-B-GallactatePRPPTranscription factor p65GlycolysisOncogene Induced SenescenceOAAIL8Canonical NF-KB PathwayGLUT1SIRT2ADP/ATPSIRT5NAMPTpyruvateIL1BPGMNMNAT2AMPKa1MalateHuRIL-10HMGA1p16NADHMDH1NMNCCL27SCO2GOT1Fatty AcidBeta OxidationSIRT3AspartateTP53NADp21pRBp38 MAPKGLUT4GOT2MDH2IL6SIRT1TNF-aG6PDHHigh proinflammatory SASP5MalateOAAAspartateMitochondrial Oxidative PhosphorylationTCA Cycle5NAD/NADHOncogene Induced SenescenceMitochondrial Dysfunction-Associated Senescence


Description

The uppermost part of the pathway includes part of the general NAM salvage pathway in the cytosol as it is relevant to senescence-induced changes to NAD metabolism. In this pathway, NAD levels are maintained through recycling back to NAD from nicotinamide (NAM) and nicotinamide mononucleotide (NMN) (Braidy et al., 2019). The conversion from NAM to NMN is catalyzed by nicotinamide phosphoribosyltransferase (NAMPT), while the conversion from NMN to NAD is catalyzed by nicotinamide mononucleotide adenylyl transferases (NMNATs). Other sources, such as nicotinic acid (NA) and nicotinamid riboside (NR), are not shown here as they are not affected by senescence, at least from current research. OIS-specific interactions are highlighted in orange, while MiDAS-specific interactions are highlighted in purple. General interactions for both (or other senescent types) remain a black color.

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Ontology Terms

 

Bibliography

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  1. Lee SM, Dho SH, Ju SK, Maeng JS, Kim JY, Kwon KS; ''Cytosolic malate dehydrogenase regulates senescence in human fibroblasts.''; Biogerontology, 2012 PubMed Europe PMC Scholia
  2. Han X, Tai H, Wang X, Wang Z, Zhou J, Wei X, Ding Y, Gong H, Mo C, Zhang J, Qin J, Ma Y, Huang N, Xiang R, Xiao H; ''''; , PubMed Europe PMC Scholia
  3. Ohanna M, Giuliano S, Bonet C, Imbert V, Hofman V, Zangari J, Bille K, Robert C, Bressac-de Paillerets B, Hofman P, Rocchi S, Peyron JF, Lacour JP, Ballotti R, Bertolotto C; ''Senescent cells develop a PARP-1 and nuclear factor-{kappa}B-associated secretome (PNAS).''; Genes Dev, 2011 PubMed Europe PMC Scholia
  4. Wiley CD, Campisi J; ''From Ancient Pathways to Aging Cells-Connecting Metabolism and Cellular Senescence.''; Cell Metab, 2016 PubMed Europe PMC Scholia
  5. Wiley CD, Velarde MC, Lecot P, Liu S, Sarnoski EA, Freund A, Shirakawa K, Lim HW, Davis SS, Ramanathan A, Gerencser AA, Verdin E, Campisi J; ''Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype.''; Cell Metab, 2016 PubMed Europe PMC Scholia
  6. Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S, Aird KM, Iwasaki O, Kossenkov AV, Schultz D, Noma KI, Baur JA, Schug Z, Tang HY, Speicher DW, David G, Zhang R; ''NAD+metabolism governs the proinflammatory senescence-associated secretome.''; Nat Cell Biol, 2019 PubMed Europe PMC Scholia
  7. Takebayashi S, Tanaka H, Hino S, Nakatsu Y, Igata T, Sakamoto A, Narita M, Nakao M; ''Retinoblastoma protein promotes oxidative phosphorylation through upregulation of glycolytic genes in oncogene-induced senescent cells.''; Aging Cell, 2015 PubMed Europe PMC Scholia
  8. Horenstein AL, Sizzano F, Lusso R, Besso FG, Ferrero E, Deaglio S, Corno F, Malavasi F; ''CD38 and CD157 ectoenzymes mark cell subsets in the human corneal limbus.''; Mol Med, 2009 PubMed Europe PMC Scholia
  9. Surjana D, Halliday GM, Damian DL; ''Role of nicotinamide in DNA damage, mutagenesis, and DNA repair.''; J Nucleic Acids, 2010 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
135695view12:22, 27 October 2024EweitzRefine legend, node heights
135694view11:19, 27 October 2024EweitzFix legend, economize layout, standardize case
118987view06:52, 7 June 2021Fehrhartconnected unconnected connections and gave pathway nodes shapes
117800view14:12, 22 May 2021EweitzModified title
117799view14:11, 22 May 2021EweitzModified title
115410view11:46, 18 February 2021EgonwMade six more pathways clickable
115381view00:20, 17 February 2021KhanspersOntology Term : 'nicotinamide adenine dinucleotide metabolic pathway' added !
115380view00:18, 17 February 2021KhanspersOntology Term : 'cellular senescence pathway' added !
115379view00:17, 17 February 2021Khanspersfixed unconnected
115122view09:54, 26 January 2021MkutmonModified description
115121view09:53, 26 January 2021MkutmonModified description
115120view09:50, 26 January 2021MkutmonModified description
115119view09:46, 26 January 2021MkutmonModified description
115118view09:44, 26 January 2021MkutmonUpdate description
115117view09:27, 26 January 2021MkutmonModified description
115114view09:05, 26 January 2021PaulaP04Modified description
115110view07:37, 26 January 2021EgonwModified title
115109view07:36, 26 January 2021EgonwNormalized two Ensembl data sources
115031view16:57, 25 January 2021PaulaP04New pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADP/ATP
AMPKa1ProteinENSG00000132356 (Ensembl)
AspartateMetabolite35391 (ChEBI)
CCL27GeneProductENSG00000213927 (Ensembl)
Canonical NF-KB PathwayPathwayWP4562 (WikiPathways)
Fatty Acid Beta OxidationPathwayWP143 (WikiPathways)
G6PDHProteinENSG00000160211 (Ensembl)
GLUT1ProteinENSG00000117394 (Ensembl)
GLUT4ProteinENSG00000181856 (Ensembl)
GOT1GeneProductENSG00000120053 (Ensembl)
GOT2GeneProductENSG00000125166 (Ensembl)
GlycolysisPathwaymap00010 (KEGG Pathway)
HMGA1GeneProductENSG00000137309 (Ensembl)
HuRProteinENSG00000066044 (Ensembl)
IL-10ProteinENSGALG00000000892 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IL6GeneProductENSG00000136244 (Ensembl)
IL8MetaboliteCHEBI:138181 (ChEBI)
MDH1GeneProductENSG00000014641 (Ensembl)
MDH2GeneProductENSG00000146701 (Ensembl)
MalateMetaboliteCHEBI:30797 (ChEBI)
Mitochondrial Oxidative PhosphorylationPathwayWP623 (WikiPathways)
NAD/NADH
NADHMetaboliteHMDB01487 (HMDB)
NADMetaboliteHMDB00902 (HMDB)
NAMPTGeneProductENSG00000105835 (Ensembl)
NMNAT2GeneProductENSG00000157064 (Ensembl)
NMNMetaboliteCHEBI:16171 (ChEBI)
OAAMetaboliteCHEBI:132560 (ChEBI)
Oncogene Induced SenescencePathwayWP3308 (WikiPathways)
Oncogene Induced SenescencePathwayWP3308 (WikiPathways)
PARP1GeneProductENSG00000143799 (Ensembl)
PGMMetaboliteCHEBI:33365 (ChEBI)
PRPPMetaboliteCHEBI:17111 (ChEBI)
SA-B-Gal
SCO2GeneProductENSG00000130489 (Ensembl)
SIRT1GeneProductENSG00000096717 (Ensembl)
SIRT2GeneProductENSG00000068903 (Ensembl)
SIRT3GeneProductENSG00000142082 (Ensembl)
SIRT5GeneProductENSG00000124523 (Ensembl)
TCA CyclePathwayWP78 (WikiPathways)
TNF-aProteinENSG000002328 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
Transcription factor p65ProteinQ04206 (Uniprot-TrEMBL)
lactateMetaboliteCHEBI:24996 (ChEBI)
nicotinamideMetaboliteCHEBI:17154 (ChEBI)
p16
p21
p38 MAPKGeneProductQ3C2E3 (Uniprot-TrEMBL)
pRBRnaENSG00000139687 (Ensembl)
pyruvateMetaboliteCHEBI:15361 (ChEBI)

Annotated Interactions

No annotated interactions

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