The Phospholipid Flippase ATP8B1 is Involved in the Pathogenesis of Ulcerative Colitis via Establishment of Intestinal Barrier Function.

Aims: Patients with mutations in ATP8B1 develop progressive familial intrahepatic cholestasis type 1 [PFIC1], a severe liver disease that requires life-saving liver transplantation. PFIC1 patients also present with gastrointestinal problems, including intestinal inflammation and diarrhoea, which are aggravated after liver transplantation. Here we investigate the intestinal function of ATP8B1 in relation to inflammatory bowel diseases.

Bile salt signaling and bile salt-based therapies in cardiometabolic disease.

Bile salts have an established role in the emulsification and intestinal absorption of dietary lipids, and their homeostasis is tightly controlled by various transporters and regulators in the enterohepatic circulation. Notably, emerging evidence points toward bile salts as major modulators of cardiometabolic disease (CMD), an umbrella disease of disorders affecting the heart and blood vessels that is caused by systemic metabolic diseases such as Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), the latter encompassing also metabolic dysfunction-associated steatohepatitis (MASH). The underlying mechanisms of protective effects of bile salts are their hormonal properties, enabling them to exert versatile metabolic effects by activating various bile salt-responsive signaling receptors with the nuclear farnesoid X receptor (FXR) and the Takeda G-protein-coupled receptor 5 (TGR5) as most extensively investigated.

ATP8B1 Deficiency Results in Elevated Mitochondrial Phosphatidylethanolamine Levels and Increased Mitochondrial Oxidative Phosphorylation in Human Hepatoma Cells.

ATP8B1 is a phospholipid flippase that is deficient in patients with progressive familial intrahepatic cholestasis type 1 (PFIC1). PFIC1 patients suffer from severe liver disease but also present with dyslipidemia, including low plasma cholesterol, of yet unknown etiology. Here we show that ATP8B1 knockdown in HepG2 cells leads to a strong increase in the mitochondrial oxidative phosphorylation (OXPHOS) without a change in glycolysis.

The phospholipid flippase ATP8B1 is required for lysosomal fusion in macrophages.

ATP8B1 is a phospholipid flippase and member of the type 4 subfamily of P-type ATPases (P4-ATPase) subfamily. P4-ATPases catalyze the translocation of phospholipids across biological membranes, ensuring proper membrane asymmetry, which is crucial for membrane protein targeting and activity, vesicle biogenesis, and barrier function. Here we have investigated the role of ATP8B1 in the endolysosomal pathway in macrophages.