Lipophagy (Homo sapiens)

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1, 2, 53, 43, 43, 43, 43cytosollipid dropletPRKAG2 p-PLINs:HSPA8p-PLINs:HSPA8:PRKAA2HSPA8 PRKAA2 PLIN2 PRKAG3 PRKAA2 HSPA8 AMPK-alpha2:AMPK-beta:AMPK-gamma:AMPPLINs on lipiddroplet surfacePRKAB1 PRKAG1 AMP p-PLINs:HSPA8p-PLIN3 p-PLIN3 HSPA8 PLIN2 PLIN3 HSPA8 PLIN3 p-PLIN2 ATPPRKAA2PLIN3 p-T172-PRKAA2 PLINs:HSPA8:PRKAA2ADPHSPA8p-PLIN2 p-PLIN2 PLINs:HSPA8HSPA8 PRKAB2 p-PLIN3 PLIN2


Description

Triglycerides stored in lipid droplets are hydrolysed under nutrient starvation to release fatty acids for energy. The content of lipid droplets may vary but they are all coated with a protective protein called perilipin. When this protein is degraded, lipid droplets associate with autophagic components and breakdown into fatty acids (Ward C et al. 2016, Schulze R J et al. 2017). This process is termed as lipophagy (Singh R et al. 2009). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 9613354
Reactome-version 
Reactome version: 73
Reactome Author 
Reactome Author: Varusai, Thawfeek

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Ontology Terms

 

Bibliography

  1. Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ.; ''Autophagy regulates lipid metabolism.''; PubMed Europe PMC Scholia
  2. Ward C, Martinez-Lopez N, Otten EG, Carroll B, Maetzel D, Singh R, Sarkar S, Korolchuk VI.; ''Autophagy, lipophagy and lysosomal lipid storage disorders.''; PubMed Europe PMC Scholia
  3. Kaushik S, Cuervo AM.; ''Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis.''; PubMed Europe PMC Scholia
  4. Kaushik S, Cuervo AM.; ''AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA.''; PubMed Europe PMC Scholia
  5. Schulze RJ, Sathyanarayan A, Mashek DG.; ''Breaking fat: The regulation and mechanisms of lipophagy.''; PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
114785view16:28, 25 January 2021ReactomeTeamReactome version 75
113230view11:29, 2 November 2020ReactomeTeamReactome version 74
112801view17:56, 9 October 2020DeSlOntology Term : 'fatty acid metabolic pathway' added !
112751view16:15, 9 October 2020ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:456216 (ChEBI)
AMP MetaboliteCHEBI:16027 (ChEBI)
AMPK-alpha2:AMPK-beta:AMPK-gamma:AMPComplexR-HSA-1454683 (Reactome)
ATPMetaboliteCHEBI:30616 (ChEBI)
HSPA8 ProteinP11142 (Uniprot-TrEMBL)
HSPA8ProteinP11142 (Uniprot-TrEMBL)
PLIN2 ProteinQ99541 (Uniprot-TrEMBL)
PLIN3 ProteinO60664 (Uniprot-TrEMBL)
PLINs on lipid droplet surfaceComplexR-HSA-9613328 (Reactome)
PLINs:HSPA8:PRKAA2ComplexR-HSA-9613508 (Reactome)
PLINs:HSPA8ComplexR-HSA-9613350 (Reactome)
PRKAA2 ProteinP54646 (Uniprot-TrEMBL)
PRKAA2ProteinP54646 (Uniprot-TrEMBL)
PRKAB1 ProteinQ9Y478 (Uniprot-TrEMBL)
PRKAB2 ProteinO43741 (Uniprot-TrEMBL)
PRKAG1 ProteinP54619 (Uniprot-TrEMBL)
PRKAG2 ProteinQ9UGJ0 (Uniprot-TrEMBL)
PRKAG3 ProteinQ9UGI9 (Uniprot-TrEMBL)
p-PLIN2 ProteinQ99541 (Uniprot-TrEMBL)
p-PLIN3 ProteinO60664 (Uniprot-TrEMBL)
p-PLINs:HSPA8:PRKAA2ComplexR-HSA-9613547 (Reactome)
p-PLINs:HSPA8ComplexR-HSA-9613533 (Reactome)
p-PLINs:HSPA8ComplexR-HSA-9620192 (Reactome)
p-T172-PRKAA2 ProteinP54646 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-9613530 (Reactome)
AMPK-alpha2:AMPK-beta:AMPK-gamma:AMPmim-catalysisR-HSA-9613530 (Reactome)
ATPR-HSA-9613530 (Reactome)
HSPA8R-HSA-9613352 (Reactome)
PLINs on lipid droplet surfaceR-HSA-9613352 (Reactome)
PLINs:HSPA8:PRKAA2ArrowR-HSA-9613513 (Reactome)
PLINs:HSPA8:PRKAA2R-HSA-9613530 (Reactome)
PLINs:HSPA8ArrowR-HSA-9613352 (Reactome)
PLINs:HSPA8R-HSA-9613513 (Reactome)
PRKAA2ArrowR-HSA-9613565 (Reactome)
PRKAA2R-HSA-9613513 (Reactome)
R-HSA-9613352 (Reactome) Lipophagy is the process of autophagic degradation of lipid droplets into fatty acids. A key step in this process is the elimination of perilipin (PLIN) proteins on lipid droplet surface. This mechanism is initiated when the cytosolic Heat shock cognate 71 kDa protein (HSPA8) binds PLIN2 and PLIN3 on the lipid droplet surface. Consequently, perilipins are phosphorylated and targeted to degradation making the lipid available for hydrolysis (S Kaushik et al. 2015). Experiments confirming this interaction were performed in rats.
R-HSA-9613513 (Reactome) Lipophagy is the process of autophagic degradation of lipid droplets into fatty acids. Lipid droplets are coated with perilipin (PLIN) protiens and they need to be eliminated for the degradation of the lipids inside. Cytosolic Heat shock cognate 71 kDa protein (HSPA8) binds PLIN2 and PLIN3 on the lipid droplet surface. Consequently, PRKAA2 bind and phosphorylate perilipins targeting them for lipophagy (S Kaushik et al. 2015, S Kaushik et al. 2016). Experiments confirming this interaction were performed in mouse.
R-HSA-9613530 (Reactome) Lipophagy is the process of autophagic degradation of lipid droplets into fatty acids. Lipid droplets are coated with perilipin (PLIN) proteins and they need to be eliminated for the degradation of the lipids inside. Cytosolic Heat shock cognate 71 kDa protein (HSPA8) binds PLIN2 and PLIN3 on the lipid droplet surface. Subsequently, AMPK binds and phosphorylates perilipins targeting them for lipophagy (S Kaushik et al. 2015, S Kaushik et al. 2016). The precise phosphorylation site(s) on PLINs are unknown. Experiments confirming this finding were performed in mouse models.
R-HSA-9613565 (Reactome) Once phosphorylated, PLINs are believed to dissociate from PRKAA2 and translocate to the cytosol (S Kaushik et al. 2015, S Kaushik et al. 2016). The precise dissociation mechanism of Plins is unclear. The experiments showing this finding were performed in mouse models.
R-HSA-9613666 (Reactome) Lipophagy is the process of autophagic degradation of lipid droplets into fatty acids. Lipid droplets are coated with perilipin (PLIN) proteins and they need to be eliminated for the degradation of the lipids inside. Cytosolic Heat shock cognate 71 kDa protein (HSPA8) binds PLIN2 and PLIN3 on the lipid droplet surface. Subsequently, PRKAA2 binds and phosphorylates perilipins. Phosphorylated PLINs dissociate from PRKAA2 and are believed to translocate to the cytosol (S Kaushik et al. 2015, S Kaushik et al. 2016). Experiments suggesting this event were performed in mouse models.
p-PLINs:HSPA8:PRKAA2ArrowR-HSA-9613530 (Reactome)
p-PLINs:HSPA8:PRKAA2R-HSA-9613565 (Reactome)
p-PLINs:HSPA8ArrowR-HSA-9613565 (Reactome)
p-PLINs:HSPA8ArrowR-HSA-9613666 (Reactome)
p-PLINs:HSPA8R-HSA-9613666 (Reactome)
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