DFCP1 is a Regulator of ATGL-mediated Lipid Droplet Lipolysis
Ismail, V.; Schuetz, M.; Castillo-Badillo, J.; Naismith, T.; Kast, D. J.
Show abstract
Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks, and therefore play a central role in cellular metabolism. Double FYVE Domain Containing Protein 1 (DFCP1/ZFYV1) has emerged as a key regulator of LD metabolism, where the nucleotide-dependent accumulation of DFCP1 on LDs influences their size, number, and dynamics. Here we show that DFCP1 regulates lipid metabolism by directly modulating the activity of Adipose Triglyceride Lipase (ATGL/PNPLA2), the rate-limiting lipase driving the catabolism of LDs. We show through pharmacological inhibition of key enzymes associated with LD metabolism that DFCP1 specifically regulates lipolysis and, to a lesser extent, lipophagy. Consistent with this observation, DFCP1 interacts with and recruits ATGL to LDs in starved cells, irrespective of known regulatory factors of ATGL. We further establish that this interaction prevents dynamic disassociation of ATGL from LDs and thereby impedes the rate of LD lipolysis. Collectively, our findings indicate that DFCP1 primes ATGL on LDs to promote rapid LD catabolism.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Up-regulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain 96%
- Multiple roles for the ESCRT machinery in maintaining plasma membrane homeostasis 95%
- Ccr4-Not ubiquitin ligase signaling regulates ribosomal protein homeostasis and inhibits 40S ribosomal autophagy 95%
Similar papers in this journal
- Insulin promoted mobilization of GLUT4 from a perinuclear storage site requires RAB10. 96%
- The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and Cilia to Regulate Ciliogenesis and Ciliary Protein Traffic 94%
- The LCLAT1/LYCAT acyltransferase is required for EGF-mediated phosphatidylinositol-3,4,5-trisphosphate generation and Akt signalling 94%
Similar papers in this journal
- A concerted mechanism involving ACAT and SREBPs by which oxysterols deplete accessible cholesterol to restrict microbial infection 95%
- Legionella pneumophila modulates host energy metabolism by ADP-ribosylation of ADP/ATP translocases 94%
- Metabolic regulation of misfolded protein import into mitochondria 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.