| Title : alpha\/beta Hydrolase Domain-containing 6 (ABHD6) Degrades the Late Endosomal\/Lysosomal Lipid Bis(monoacylglycero)phosphate - Pribasnig_2015_J.Biol.Chem_290_29869 |
| Author(s) : Pribasnig MA , Mrak I , Grabner GF , Taschler U , Knittelfelder O , Scherz B , Eichmann TO , Heier C , Grumet L , Kowaliuk J , Romauch M , Holler S , Anderl F , Wolinski H , Lass A , Breinbauer R , Marsche G , Brown JM , Zimmermann R |
| Ref : Journal of Biological Chemistry , 290 :29869 , 2015 |
| Abstract : alpha/beta Hydrolase domain-containing 6 (ABHD6) can act as monoacylglycerol hydrolase and is believed to play a role in endocannabinoid signaling as well as in the pathogenesis of obesity and liver steatosis. However, the mechanistic link between gene function and disease is incompletely understood. Here we aimed to further characterize the role of ABHD6 in lipid metabolism. We show that mouse and human ABHD6 degrade bis(monoacylglycero)phosphate (BMP) with high specific activity. BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes/lysosomes, where it plays a key role in the formation of intraluminal vesicles and in lipid sorting. Up to now, little has been known about the catabolism of this lipid. Our data demonstrate that ABHD6 is responsible for approximately 90% of the BMP hydrolase activity detected in the liver and that knockdown of ABHD6 increases hepatic BMP levels. Tissue fractionation and live-cell imaging experiments revealed that ABHD6 co-localizes with late endosomes/lysosomes. The enzyme is active at cytosolic pH and lacks acid hydrolase activity, implying that it degrades BMP exported from acidic organelles or de novo-formed BMP. In conclusion, our data suggest that ABHD6 controls BMP catabolism and is therefore part of the late endosomal/lysosomal lipid-sorting machinery. |
| ESTHER : Pribasnig_2015_J.Biol.Chem_290_29869 |
| PubMedSearch : Pribasnig_2015_J.Biol.Chem_290_29869 |
| PubMedID: 26491015 |
| Gene_locus related to this paper: human-ABHD6 |
| Gene_locus related to this paper: human-ABHD6 |
Pribasnig MA, Mrak I, Grabner GF, Taschler U, Knittelfelder O, Scherz B, Eichmann TO, Heier C, Grumet L, Kowaliuk J, Romauch M, Holler S, Anderl F, Wolinski H, Lass A, Breinbauer R, Marsche G, Brown JM, Zimmermann R (2015)
alpha\/beta Hydrolase Domain-containing 6 (ABHD6) Degrades the Late Endosomal\/Lysosomal Lipid Bis(monoacylglycero)phosphate
Journal of Biological Chemistry
290 :29869
Pribasnig MA, Mrak I, Grabner GF, Taschler U, Knittelfelder O, Scherz B, Eichmann TO, Heier C, Grumet L, Kowaliuk J, Romauch M, Holler S, Anderl F, Wolinski H, Lass A, Breinbauer R, Marsche G, Brown JM, Zimmermann R (2015)
Journal of Biological Chemistry
290 :29869