Abstract:
:Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are critically involved in the maintenance of energy homeostasis. Hypoxia-inducible lipid droplet-associated protein (HILPDA)/hypoxia-inducible gene-2 (Hig-2) has been shown to affect intracellular TAG levels, yet, the underlying molecular mechanisms are unclear. Here, we show that HILPDA inhibits adipose triglyceride lipase (ATGL), the enzyme catalyzing the first step of intracellular TAG hydrolysis. HILPDA shares structural similarity with G0/G1 switch gene 2 (G0S2), an established inhibitor of ATGL. HILPDA inhibits ATGL activity in a dose-dependent manner with an IC50 value of ∼2 μM. ATGL inhibition depends on the direct physical interaction of both proteins and involves the N-terminal hydrophobic region of HILPDA and the N-terminal patatin domain-containing segment of ATGL. Finally, confocal microscopy combined with Förster resonance energy transfer-fluorescence lifetime imaging microscopy analysis indicated that HILPDA and ATGL colocalize and physically interact intracellularly. These findings provide a rational biochemical explanation for the tissue-specific increased TAG accumulation in HILPDA-overexpressing transgenic mouse models.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Padmanabha Das KM,Wechselberger L,Liziczai M,De la Rosa Rodriguez M,Grabner GF,Heier C,Viertlmayr R,Radler C,Lichtenegger J,Zimmermann R,Borst JW,Zechner R,Kersten S,Oberer Mdoi
10.1194/jlr.M082388subject
Has Abstractpub_date
2018-03-01 00:00:00pages
531-541issue
3eissn
0022-2275issn
1539-7262pii
jlr.M082388journal_volume
59pub_type
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