Ectopic β-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis

  title={Ectopic $\beta$-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis},
  author={Laurent O. Martinez and S{\'e}bastien Jacquet and J. P. Est{\`e}ve and Corinne Rolland and Elena Cabezon and Eric Champagne and Thierry Pineau and V. M. Georgeaud and John E. Walker and François Tercé and Xavier Collet and Bertrand Perret and Ronald Barbaras},
The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in ‘reverse cholesterol transport. [] Key Result Here we show that this receptor is identical to the β-chain of ATP synthase, a principal protein complex of the mitochondrial inner membrane. Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface.
Research Article The nucleotide receptor P2Y 13 is a key regulator of hepatic High-Density Lipoprotein (HDL) endocytosis
Using both a pharmacological approach and small interference RNA, P2Y13 is identified as the main partner in hepatic HDL endocytosis, in cultured cells as well as in situ in perfused mouse livers and a new important action of the antithrombotic agent AR-C69931MX is found as a strong ac- tivator of P 2Y13-mediated HDL endocytetosis.
New insight on the molecular mechanisms of high-density lipoprotein cellular interactions
The last decade has seen major breakthroughs in the identification and elucidation of the role of cellular partners of HDL metabolism, and in their transcriptional regulations, opening up new perspectives in the modulation of HDL cholesterol.
Mitochondrial Inhibitory Factor 1 (IF1) Is Present in Human Serum and Is Positively Correlated with HDL-Cholesterol
The view that, in humans, circulating IF1 might affect HDL levels by inhibiting hepatic HDL uptake and also impact TG metabolism is supported.
The β-subunit of ATP synthase is involved in cellular uptake and resecretion of apoA-I but does not control apoA-I-induced lipid efflux in adipocytes
It is shown that blocking apoA-I recycling by adipocytes can be blocked by a monoclonal antibody against the β-subunit of ATP synthase, a protein that had been previously identified as an apo A-I receptor.
Nephrotic syndrome causes upregulation of HDL endocytic receptor and PDZK-1-dependent downregulation of HDL docking receptor.
  • N. Vaziri, P. Gollapudi, H. Moradi
  • Biology, Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2011
NS results in elevation of hepatic HDL endocytic receptor and deficiency of HDL docking receptor, which can increase catabolism and diminish recycling of HDL and contribute to the defective reverse cholesterol/lipid transport in NS.
ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level
The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.
Ecto-F₁-ATPase: a moonlighting protein complex and an unexpected apoA-I receptor.
The role of the F₁-ATPase pathway(s) in HDL-cholesterol uptake and apoA-I-mediated endothelial protection suggests its potential importance in reverse cholesterol transport and its regulation might represent a potential therapeutic target for HDL-related therapy for cardiovascular diseases.
Ectopic adenine nucleotide translocase activity controls extracellular ADP levels and regulates the F1-ATPase-mediated HDL endocytosis pathway on hepatocytes.
HDL biogenesis, remodeling, and catabolism.
Key features of the proteins that participate in the generated, remodeled, and catabolized in plasma are described, emphasizing how mutations in apolipoprotein A-I (apoA-I) and the other proteins affect HDL metabolism.
Scavenger Receptor BI-mediated Selective Uptake Is Required for the Remodeling of High Density Lipoprotein by Endothelial Lipase*
The results indicate that SR-BI-mediated selective uptake of HDL cholesteryl ester is essential for the remodeling of large α-migrating HDL particles by EL.


The Correlation of ATP-binding Cassette 1 mRNA Levels with Cholesterol Efflux from Various Cell Lines*
It is found that while other cell lines express ABC1 constitutively, only J774 and elicited mouse macrophages show a substantial increase of mRNA and efflux with cAMP treatment, and the stimulation of efflux exhibits specificity for apoA-I, high density lipoprotein, and other apolipoproteins as cholesterol acceptors, but not for small unilamellar vesicles, bile acid micelles, or cyclodextrin.
High density lipoprotein receptors, binding proteins, and ligands.
  • N. Fidge
  • Biology
    Journal of lipid research
  • 1999
Several HDL binding proteins, quite disparate in structure, have recently been cloned and their role in HDL metabolism is currently being assessed and growing evidence for the involvement of lipid-poor apoA-I as a mediator of such pathways is also discussed.
High Density Lipoprotein (HDL) Particle Uptake Mediated by Scavenger Receptor Class B Type 1 Results in Selective Sorting of HDL Cholesterol from Protein and Polarized Cholesterol Secretion*
High density lipoprotein particles, internalized via SR-BI, undergo a novel process of selective transcytosis, leading to polarized cholesterol transport, which is involved in uptake and degradation of apoE-free HDL in hepatocytes.
Trypsin-sensitive and Lipid-containing Sites of the Macrophage Extracellular Matrix Bind Apolipoprotein A-I and Participate in ABCA1-dependent Cholesterol Efflux*
A novel binding site for apoA-I on the macrophage ECM is established that may function together with ABCA1 in promoting cholesterol efflux and is established with re-lipidation of the ECM.
Chylomicron remnant metabolism. Role of hepatic lipoprotein receptors in mediating uptake.
It is known that this fraction contains at least three proteins, all of which bind apo E with high affinity, and a cDNA clone coding for a protein that is apparently distinct from the ATPase and the Mr congruent to 59,000 protein has been obtained from a lambda gt11 library.
Hepatic lipase induces the formation of pre-beta 1 high density lipoprotein (HDL) from triacylglycerol-rich HDL2. A study comparing liver perfusion to in vitro incubation with lipases.
The results evidence the role of the triacylglycerol lipase activity of hepatic lipase in the formation of pre-beta 1 HDL from Triacyl Glycerol-rich HDL2.
Identification of Scavenger Receptor SR-BI as a High Density Lipoprotein Receptor
It is shown that the class B scavenger receptor SR-BI is an HDL receptor, which mediates selective cholesterol uptake by a mechanism distinct from the classic LDL receptor pathway.
Remnant high density lipoprotein2 particles produced by hepatic lipase display high-affinity binding and increased endocytosis into a human hepatoma cell line (HEPG2).
It is suggested that the continuous remodeling of HDL induces different binding and internalization characteristics of the HDL particles and that the high-affinity HDL binding sites might trigger the internalization of apo HDL through the low-Affinity binding sites.
ATP-binding Cassette Transporter A1 (ABCA1) Functions as a Cholesterol Efflux Regulatory Protein*
The data suggest that the binding of apoA-I to ABCA1 leads to the formation of phospholipid-apoA- I complexes, which subsequently promote cholesterol efflux in an autocrine or paracrine fashion.
Interaction of the C-terminal domain of p43 and the alpha subunit of ATP synthase. Its functional implication in endothelial cell proliferation.
The potential interaction of p43/EMAP II with alpha-ATP synthase and its role in the proliferation of endothelial cells is suggested.