Cellular Transporter Proteins in Cholesterol Metabolism

Review Article

J Endocr Disord. 2020; 6(1): 1032.

Cellular Transporter Proteins in Cholesterol Metabolism

Sozmen EY1* and Sozmen B2

¹Department of Medical Biochemistry, Ege University, Turkey

²Department of Internal Medicine, Izmir University, Turkey

*Corresponding author: Eser Yildirim Sözmen, Ege University, Department of Medical Biochemistry, Turkey

Received: January 09, 2020; Accepted: February 19, 2020; Published: February 26, 2020


Cholesterol from sources both endogenous and exogenous is delivered by plasma membrane receptors via endocytosis. While ApoB receptors and LDL receptors bind LDL cholesterol outside of the membrane, LDL receptor adaptor proteins control these processes. Lysosomal acid lipase enzyme hydrolyzes ester cholesterol into free cholesterol in lysosome. Lysosomal cholesterol is transported to the endoplasmic reticulum, the plasma membrane, mitochondria and/or peroxisomes through integral membrane proteins (NPC-1, NPC-2) Steroidogenic Acute Regulatory Protein Related Lipid Transfer Domain-3 (STARD3), Ras superfamily and OSBP Related Proteins, (ORPs). Free cholesterol is exported by ABCA1 and ABCG1 receptors. In this mini review, all these proteins affecting cellular transport and metabolism of cholesterol will be discussed and the diseases related to deficiencies and/or defects of these proteins will be summarized. De novo synthesis and control of cholesterol metabolism are out of focus of this review.

Keywords: Cholesterol; NPC1; NPC2


ABCA1: Adenosine Triphosphate-Binding Cassette Transporter; A1; ACAT: Acyl-CoA Cholesteryl Acyl Transferase; ARH: Autosomal Recessive Hypercholesterolaemia; CESD: Cholesteryl Ester Storage Disease; EGF: Epidermal Growth Factor; ER: Endoplasmic Reticulum; ESCRT: Endosomal Sorting Complex Required For Transport; HDL: High Density Lipoprotein; HMGCR3: Hydroxy 3 Methylglutaryl Coa Reductase; LAL: Lysosomal Acid Lipase Enzyme; LAMP1: Lysosomal- Associated Membrane Protein 1; LDL: Low Density Lipoprotein; LDL: RAP1LDL Receptor Adaptor Protein1; LDL: LDL Receptor Family; LE: Late Endosome; LRP1: Alpha2 Macroglobulin Receptor or CD91; LY: Lysosome; MLN64: Endosomal Metastatic Lymph Node Protein 64; NPC1: Niemann Pick Type 1 Protein; NPC2: Niemann Pick Type C2 Protein; ORDOSBP Related Domain; ORPs OSBP: Related Proteins; ORPs OSBP: Related Proteins; OSBP: Oxysterol Binding Protein; PCSK9 Proprotein Convertase Subtilisin /Kexin Type 9; STARD3NLSTARD3 N Terminal like; STARD3 Steroidogenic Acute; Regulatory Protein Related Lipid Transfer Domain 3; START: Steroidogenic Acute Regulatory Protein; VAPVAMP Associated Protein; VLDL: Very Low Density Lipoprotein; VSMC: Vascular Smooth Muscle Cell.


Intracellular Cholesterol transport is accomplished by two main roats: vesicular and non-vesicular. Vesicular transport requires an intact cytoskeleton where cholesterol moves along cytoskeletal proteins via energy supplied by dephosphorylation of ATP. Non vesicular transport requires carrier proteins which are the subject of this review.

Cellular cholesterol is transported by various membrane proteins and free transport proteins inside cell. After endocytosis of lipoproteins, cholesteryl esters are hydrolyzed by acid lipases in lysosomes. Free cholesterol might be transported to endoplasmic reticulum, plasma membrane, mitochondria and/or peroxisome by transport proteins [1]. This process and the transport proteins which have a role in this pathway will be discussed in following order.

A. Cellular uptake of Cholesterol via endocytosis of low density lipoproteins

B. Metabolism of ester cholesterol in Lysosome; Lysosomal Acid Lipase

C. Intracellular Trafficking of Cholesterol

D. Cellular Removal of Cholesterol

A. Cellular uptake of cholesterol via endocytosis of low density lipoproteins

Cellular uptake of cholesterol via endocytosis of low density lipoproteins is achieved by collaboration of various proteins including ApoB receptor, LDL Receptor family (LDLR), LDL Receptor Adaptor Protein-1 (LDL RAP-1), Proprotein Convertase Subtilisin /Kexin Type 9 (PCSK9), and Sortilin-1.

The members of LDLR family especially; LDLR, VLDLR, LRP5/6, LRP1, and LRP2 (megalin) participate in cholesterol homeostasis and lipid metabolism. Their structure is similar to common motifs, LDLR type A repeats, Epidermal Growth Factor (EGF)-like domain, transmembrane anchor, and cytoplasmic domain. LDLR recognizes and binds apoB-100 of LDL particles VLDL, IDL, High-Density Lipoprotein (HDL), and chylomicron remnant at neutral pH [2]. LDL particles play a vital role in cholesterol homeostasis inside of cell in terms of inhibiting the gene expression of 3-Hydroxy- 3-Methylglutaryl-Coa Reductase (HMGCR), stimulating Acyl- Coa Cholesteryl Acyl Transferase (ACAT) and suppressing LDLR synthesis to reduce LDL uptake [2].

After binding of one apoB-100 LDL particle with one LDL receptor monomer, this complex undergoes endocytosis. Apo-E containing lipoproteins are also recognized and bound by VLDLR, LDLR, LRP8, LRP1, LRP2, and LRP6. While VLDLR is expressed in adipose tissue, skeletal muscle, heart, endothelial cells of capillaries, and small arterioles, LDLR is expressed in hepatocytes and LRP8 (ApoER2) in brain, testis, and placenta [2].

Citation: Sozmen EY and Sozmen B. Cellular Transporter Proteins in Cholesterol Metabolism. J Endocr Disord. 2020; 6(1): 1032.