title: ATP8B1 and ATP11C: Two Lipid Flippases Important for Hepatocyte Function.
abstract: P4 ATPases are lipid flippases and transport phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes. Lipid flipping is important for the biogenesis of transport vesicles. Recently it was shown that loss of the P4 ATPases ATP8B1 and ATP11C are associated with severe Cholestatic liver disease. Mutation of ATP8B1 cause progressive familial Intrahepatic Cholestasis type 1 (PFIC1)and benign recurrent intrahepatic cholestasis type 1 (BRIC 1). From our observations we hypothesized that ATP8B1 deficiency causes a phospholipids randomization at the canalicular membrane, which results in extraction of cholesterol due to increase sensitivity of the canalicular membrane. Deficiency of ATP11C causes conjugated hyperbilirubinemia. In our preliminary result we observed accumulation of unconjugated bile salts in Atp11c deficient mice probably because of regulation in the expression or function of OATP1B2. Similar to ATP8B1, ATP11C have regulation on membrane transporters.
authors.affiliation: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Naik
authors.forename: Dirk R
authors.initials: DR
authors.lastname: de Waart
authors.forename: Karina
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Suzanne
authors.initials: S
authors.lastname: Duijst
authors.forename: Kam Ho
authors.initials: KH
authors.lastname: Mok
authors.forename: Ronald P J
authors.initials: RP
authors.lastname: Oude Elferink
authors.forename: Piter J
authors.initials: PJ
authors.lastname: Bosma
authors.forename: Coen C
authors.initials: CC
authors.lastname: Paulusma
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000235:genetics*; D002793:Cholic Acids / Q000097:blood / Q000235:genetics; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D006932:Hyperbilirubinemia / Q000235:genetics; D051379:Mice; D009154:Mutation; D049294:Phospholipid Transfer Proteins / Q000172:deficiency / Q000235:genetics*; D043202:Steroid Metabolism, Inborn Errors / Q000235:genetics
chemical_list: D002793:Cholic Acids; D049294:Phospholipid Transfer Proteins; C000605549:ATP11C protein, mouse; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human; C491742:Atp8b1 protein, mouse