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World J Gastroenterol. Dec 21, 2010; 16(47): 5925-5935
Published online Dec 21, 2010. doi: 10.3748/wjg.v16.i47.5925
Ecto-F1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor
Pierre Vantourout, Claudia Radojkovic, Laeticia Lichtenstein, Véronique Pons, Eric Champagne, Laurent O Martinez
Pierre Vantourout, Claudia Radojkovic, Laeticia Lichtenstein, Véronique Pons, Eric Champagne, Laurent O Martinez, Institut national de la santé et de la recherche médicale U1048, Toulouse, F-31000, France
Pierre Vantourout, Claudia Radojkovic, Laeticia Lichtenstein, Véronique Pons, Eric Champagne, Laurent O Martinez, Institute of Metabolic and Cardiovascular Diseases, Université Toulouse III Paul-Sabatier, Toulouse, F-31300, France
Author contributions: Vantourout P and Martinez LO contributed extensively to all sections presented in this paper; Radojkovic C, Lichtenstien L and Champagne E contributed to the section “A new localization for many new roles: ecto-F1-ATPase as a moonlighting protein”; Pons V contributed to the section “An unexpected and so far unexplained localization”.
Supported by An INSERM Avenir Grant (Martinez LO), ANR (Martinez LO and Lichtenstein L, #GENO 102 01) and the French Association pour la Recherche sur le Cancer (Vantourout P and Champagne E, #3711-3913-4847); An INSERM young scientist fellowship (Pons V)
Correspondence to: Laurent O Martinez, PhD, Institut national de la santé et de la recherche médicale U1048, Toulouse, F-31000, France. laurent.martinez@inserm.fr
Telephone: +33-562-748670 Fax: +33-562-748666
Received: July 2, 2010
Revised: November 11, 2010
Accepted: November 18, 2010
Published online: December 21, 2010
Abstract

Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ecto-F1-ATPase. Particularly, 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. Therefore, it is timely for us to better understand how this ecto-enzyme and downstream pathways are regulated and to develop pharmacologic interventions.

Keywords: F1Fo ATP synthase; High density lipoproteins receptor; Apolipoprotein A-I; Purinergic receptor P2Y13; Adenylate kinase; Nucleotide; Endothelium; Antitumor immunity