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

Laurent O. Martinez, Sébastien Jacquet, Jean-Pierre Esteve, Corinne Rolland, Elena Cabezón, Eric Champagne, Thierry Pineau, Valérie Georgeaud, John E. Walker, François Tercé, Xavier Collet, Bertrand Perret and Ronald Barbaras ()
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Laurent O. Martinez: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques
Sébastien Jacquet: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques
Jean-Pierre Esteve: Institut Fédératif de Recherche Louis Bugnard, IFR 31, Institut National de la Santé et de la Recherche Médicale, Unité 531, Biologie et Pathologie Digestive, Hôpital Rangueil
Corinne Rolland: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques
Elena Cabezón: Medical Research Council Dunn Human Nutrition Unit
Eric Champagne: Département Immunologie Moléculaire et Biologie du Lymphocyte T
Thierry Pineau: Institut National de la Recherche Agronomique, Laboratoire de Pharmacologie et Toxicologie
Valérie Georgeaud: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques
John E. Walker: Medical Research Council Dunn Human Nutrition Unit
François Tercé: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques
Xavier Collet: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques
Bertrand Perret: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques
Ronald Barbaras: Institut Fédératif de Recherche Claude de Preval, IFR 30, Institut National de la Santé et de la Recherche Médicale, Unité 563, Département Lipoprotéines, et Médiateurs Lipidiques

Nature, 2003, vol. 421, issue 6918, 75-79

Abstract: Abstract The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in ‘reverse cholesterol transport’1. In this process, HDL particles mediate the efflux and the transport of cholesterol from peripheral cells to the liver for further metabolism and bile excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis2. A high-affinity HDL receptor for apolipoprotein A-I (apoA-I) was previously identified on the surface of hepatocytes3,4. 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. Receptor stimulation by apoA-I triggers the endocytosis of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly on the generation of ADP. We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound ATP synthase has a previously unsuspected role in modulating the concentrations of extracellular ADP and is regulated by a principal plasma apolipoprotein.

Date: 2003
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DOI: 10.1038/nature01250

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