ABCA1 and nascent HDL biogenesis

• Published in: BioFactors (Oxford) Vol. 40; no. 6; pp. 547 - 554
• Main Authors: Wang, Shuhui, Smith, Jonathan D.
• Format: Journal Article
• Language: English
• Published: Netherlands Blackwell Publishing Ltd 01.11.2014
• Subjects: ABCA1; Animals; apoAI; Apolipoprotein A-I - genetics; Apolipoprotein A-I - metabolism; atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; ATP Binding Cassette Transporter 1 - genetics; ATP Binding Cassette Transporter 1 - metabolism; Biological Transport; Cell Membrane - chemistry; Cell Membrane - metabolism; Cholesterol Esters - metabolism; Gene Expression Regulation; high-density lipoprotein; Homeostasis; Humans; Lipid Droplets - chemistry; Lipid Droplets - metabolism; Lipid Metabolism; Lipoproteins, HDL - biosynthesis; Lipoproteins, HDL - blood; reverse cholesterol transport; Signal Transduction; Tangier Disease - genetics; Tangier Disease - metabolism; Tangier Disease - pathology; ABCA1; atherosclerosis; reverse cholesterol transport; apoAI; high-density lipoprotein
• ISSN: 0951-6433; 1872-8081; 1872-8081
• DOI: 10.1002/biof.1187

ABCA1 mediates the secretion of cellular free cholesterol and phospholipids to an extracellular acceptor, apolipoprotein AI, to form nascent high‐density lipoprotein (HDL). Thus, ABCA1 is a key molecule in cholesterol homeostasis. Functional studies of certain Tangier disease mutations demonstrate that ABCA1 has multiple activities, including plasma membrane remodeling and apoAI binding to cell surface, which participate in nascent HDL biogenesis. Recent advances in our understanding of ABCA1 have demonstrated that ABCA1also mediates unfolding the N terminus of apoAI on the cell surface, followed by lipidation of apoAI and release of nascent HDL. Although ABCA1‐mediated cholesterol efflux to apoAI can occur on the plasma membrane, the role of apoAI retroendocytosis during cholesterol efflux may play a role in macrophage foam cells that store cholesterol esters in cytoplasmic lipid droplets. © 2014 BioFactors, 40(6):547–554, 2014