It takes a village: channeling fatty acid metabolism and triacylglycerol formation via protein interactomes.
acyl-coenzyme A
beta oxidation
de novo lipogenesis
lipid droplets
Journal
Journal of lipid research
ISSN: 1539-7262
Titre abrégé: J Lipid Res
Pays: United States
ID NLM: 0376606
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
17
12
2018
revised:
14
01
2019
pubmed:
27
1
2019
medline:
18
6
2020
entrez:
27
1
2019
Statut:
ppublish
Résumé
Diet, hormones, gene transcription, and posttranslational modifications control the hepatic metabolism of FAs; metabolic dysregulation causes chronic diseases, including cardiovascular disease, and warrants exploration into the mechanisms directing FA and triacylglycerol (TAG) synthesis and degradation. Long-chain FA metabolism begins by formation of an acyl-CoA by a member of the acyl-CoA synthetase (ACSL) family. Subsequently, TAG synthesis begins with acyl-CoA esterification to glycerol-3-phosphate by a member of the glycerol-3-phosphate acyltransferase (GPAT) family. Our studies of the isoforms ACSL1 and GPAT1 strongly suggest that these proteins are members of larger protein assemblies (interactomes). ACSL1 targeted to the ER interacts with peroxisomal, lipid droplet, and tethering proteins, uncovering a dynamic role for ACSL1 in organelle and lipid droplet interactions. On the outer mitochondrial membrane (OMM), PPARα upregulates ACSL1, which interacts with proteins believed to tether lipid droplets to the OMM. In contrast, GPAT1 is upregulated nutritionally by carbohydrate and insulin in a coordinated sequence of enzyme reactions, from saturated FA formation via de novo lipogenesis to FA esterification by GPAT1 and entry into the TAG biosynthesis pathway. We propose that involved enzymes form a dynamic protein interactome that facilitates esterification and that other lipid-metabolizing pathways will exist in similar physiologically regulated interactomes.
Identifiants
pubmed: 30683668
pii: S0022-2275(20)32612-2
doi: 10.1194/jlr.S091843
pmc: PMC6399496
doi:
Substances chimiques
Fatty Acids
0
Triglycerides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
490-497Informations de copyright
Copyright © 2019 Coleman.
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