Lipid particle organization (Homo sapiens)

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cytosollipid dropletendoplasmic reticulum lumenHILPDA:lipid dropletPL CIDEA:CIDECCIDEC CIDEC PL (FITM1,FITM2):TAGsTAG CHEST PL CHEST TAGFITM2 HILPDA CHEST HILPDACIDEA:CIDEC:lipiddropletHSD17B13 CIDEA PL HSD17B13:lipiddropletCIDEA FITM1,FITM2TAG TAG FITM2 HSD17B13CHEST TAG FITM1 FITM1 lipid dropletTAG


Description

Lipid droplets (LDs) are cytosolic structures found in cells of all eukaryotes, comprising a monolayer of phospholipids surrounding a core of uncharged lipids such as triglyceride (TAG) and sterol esters. CIDEA, CIDEB and CIDEC were first studied for their roles in promotion of apoptosis but they are also known to play a role in energy metabolism. CIDEA and C bind to lipid droplets and regulate their enlargement, thereby restricting lipolysis and favouring storage (by promoting net neutral lipid transfer from smaller to larger lipid droplets) (Gao & Goodman 2015). LD formation involves the partitioning of neutral lipids from their site of synthesis at the endoplasmic reticulum (ER) to the cytosol. The fat storage-inducing transmembrane proteins 1 and 2 (FITM1 and FITM2), associated with the ER membrane, mediate binding and partitioning of TAGs into LDs. The short-chain dehydrogenases/reductases (SDR) family is a large family of NAD- or NADP-dependent oxidoreductase enzymes. 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) is a recently-discovered enzyme of unknown physiological function that is associated with lipid droplets and significantly upregulated in patients with nonalcoholic fatty liver disease. Hypoxia-inducible lipid droplet-associated protein (HILPDA) is a lipid droplet protein and stimulates intracellular lipid accumulation. View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8964572
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Jassal, Bijay

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History

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CompareRevisionActionTimeUserComment
114765view16:25, 25 January 2021ReactomeTeamReactome version 75
113209view11:27, 2 November 2020ReactomeTeamReactome version 74
112433view15:37, 9 October 2020ReactomeTeamReactome version 73
101338view11:22, 1 November 2018ReactomeTeamreactome version 66
100876view20:56, 31 October 2018ReactomeTeamreactome version 65
100417view19:30, 31 October 2018ReactomeTeamreactome version 64
99967view16:14, 31 October 2018ReactomeTeamreactome version 63
99521view14:49, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93314view11:20, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
(FITM1,FITM2):TAGsComplexR-HSA-8857661 (Reactome)
CHEST MetaboliteCHEBI:17002 (ChEBI)
CIDEA ProteinO60543 (Uniprot-TrEMBL)
CIDEA:CIDEC:lipid dropletComplexR-HSA-8856647 (Reactome)
CIDEA:CIDECComplexR-HSA-8856629 (Reactome)
CIDEC ProteinQ96AQ7 (Uniprot-TrEMBL)
FITM1 ProteinA5D6W6 (Uniprot-TrEMBL)
FITM1,FITM2ComplexR-HSA-8857666 (Reactome)
FITM2 ProteinQ8N6M3 (Uniprot-TrEMBL)
HILPDA ProteinQ9Y5L2 (Uniprot-TrEMBL)
HILPDA:lipid dropletComplexR-HSA-8858282 (Reactome)
HILPDAProteinQ9Y5L2 (Uniprot-TrEMBL)
HSD17B13 ProteinQ7Z5P4 (Uniprot-TrEMBL)
HSD17B13:lipid dropletComplexR-HSA-8862370 (Reactome)
HSD17B13ProteinQ7Z5P4 (Uniprot-TrEMBL)
PL MetaboliteCHEBI:16247 (ChEBI)
TAG MetaboliteCHEBI:17855 (ChEBI)
TAGMetaboliteCHEBI:17855 (ChEBI)
lipid dropletComplexR-ALL-8866926 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
(FITM1,FITM2):TAGsArrowR-HSA-8857686 (Reactome)
CIDEA:CIDEC:lipid dropletArrowR-HSA-8856630 (Reactome)
CIDEA:CIDECR-HSA-8856630 (Reactome)
FITM1,FITM2R-HSA-8857686 (Reactome)
HILPDA:lipid dropletArrowR-HSA-8858270 (Reactome)
HILPDAR-HSA-8858270 (Reactome)
HSD17B13:lipid dropletArrowR-HSA-8862380 (Reactome)
HSD17B13R-HSA-8862380 (Reactome)
R-HSA-8856630 (Reactome) Humans possess three cell death-inducing DFFA-like effector (CIDE) proteins, CIDEA, CIDEB and CIDEC. Initially, their function was determined to be the promotion of apoptosis but they are also known to play a role in energy metabolism. CIDEA and C bind to lipid droplets and regulate their enlargement, thereby restricting lipolysis and favouring storage (by promoting net neutral lipid transfer from smaller to larger lipid droplets) (for review see Gao & Goodman 2015). CIDEA is bound to CIDEC to form a heterodimer (Liu et al. 2009). CIDEB has not been determined to bind lipid droplets.
R-HSA-8857686 (Reactome) Lipid droplets (LDs) are cytosolic structures found in cells of all eukaryotes, comprising a monolayer of phospholipids surrounding a core of uncharged lipids such as triglyceride (TAG) and sterol esters. They play an important role in both cellular physiology and disease. LD formation involves the partitioning of neutral lipids from their site of synthesis at the endoplasmic reticulum (ER) to the cytosol. The fat storage-inducing transmembrane proteins 1 and 2 (FITM1 and FITM2) belong to an evolutionarily-conserved gene family which mediates LD formation (Kadereit et al. 2008, Gross et al. 2011). FITM1 and FITM2 are ER membrane associated proteins that mediate binding and partitioning of TAGs into LDs (Gross et al. 2011, Miranda et al. 2014). In mammals, FITM1 is expressed primarily in skeletal muscle whereas FITM2 is expressed primarily in adipose tissue, suggesting these proteins may have unique functions (Gross et al. 2011).
R-HSA-8858270 (Reactome) Hypoxia-inducible lipid droplet-associated protein (HILPDA aka HIG2) was first described as a novel gene inducible by hypoxia and glucose deprivation, but its function and mechanisms of regulation remain unknown. HILPDA is a novel lipid droplet (LD) protein and stimulates intracellular lipid accumulation, which may play an important functional role in diseases associated with pathological lipid accumulation (Gimm et al. 2010, Carr & Ahima 2016).
R-HSA-8862380 (Reactome) The short-chain dehydrogenases/reductases (SDR) family is a large family of NAD- or NADP-dependent oxidoreductase enzymes. 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) is a recently-discovered member of this family whose physiological function is unknown (Liu et al. 2007). It has, however, been found to associate with lipid droplets and is significantly upregulated in patients with nonalcoholic fatty liver disease (NAFLD) which is characterised by an accumulation of lipid droplets in the liver. In a murine model of fatty liver and diabetes, mice with fatty livers show upregulated expression of HSD17B13, suggesting a pathogenic role for HSD17B13 in NAFLD development (Su et al. 2014).
TAGR-HSA-8857686 (Reactome)
lipid dropletR-HSA-8856630 (Reactome)
lipid dropletR-HSA-8858270 (Reactome)
lipid dropletR-HSA-8862380 (Reactome)
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