cholesterol import

Definition

Target type: biologicalprocess

The directed movement of cholesterol into a cell or organelle. [GOC:BHF, GOC:rl]

Cholesterol import is a critical process for cells to obtain cholesterol, an essential component of cell membranes, steroid hormone synthesis, and other vital functions. It involves a complex interplay of proteins and lipids, and can be broadly divided into two main pathways:

**1. Receptor-mediated endocytosis (RME) of low-density lipoprotein (LDL):**

* **LDL binding and internalization:** LDL particles, which are rich in cholesterol esters, bind to LDL receptors (LDLR) located on the cell surface. This binding triggers the formation of clathrin-coated pits, invaginations of the plasma membrane that encapsulate LDL-LDLR complexes.
* **Endocytosis and vesicle transport:** The clathrin-coated pits pinch off to form clathrin-coated vesicles, which carry the LDL-LDLR complexes into the cell. These vesicles then fuse with early endosomes, acidic compartments within the cell.
* **LDL dissociation and receptor recycling:** The acidic environment within the early endosomes promotes the dissociation of LDL from the LDLR. The LDLR is recycled back to the cell surface, while the LDL particle is transported to late endosomes.
* **Lysosomal degradation and cholesterol release:** The late endosomes fuse with lysosomes, the cell's degradative organelles. Within lysosomes, enzymes hydrolyze the cholesterol esters in LDL, releasing free cholesterol.
* **Cholesterol transport:** The free cholesterol is then transported to other cellular compartments, such as the endoplasmic reticulum (ER) and the plasma membrane, where it is utilized for various functions.

**2. Non-receptor-mediated uptake of cholesterol:**

* **Free cholesterol uptake:** Cells can also take up free cholesterol directly from the extracellular environment via passive diffusion or facilitated diffusion. Specific transport proteins, such as Niemann-Pick C1 (NPC1), mediate this uptake.
* **Esterification:** Once inside the cell, free cholesterol can be esterified by acyl-coenzyme A:cholesterol acyltransferase (ACAT) to form cholesterol esters, a storage form of cholesterol.

**3. Regulation of cholesterol import:**

* **Feedback regulation:** Cholesterol import is tightly regulated to maintain cellular cholesterol homeostasis. High levels of intracellular cholesterol can downregulate LDLR expression, reducing LDL uptake.
* **SREBP pathway:** Sterol regulatory element-binding protein (SREBP) is a key regulator of cholesterol biosynthesis and import. When cellular cholesterol levels are low, SREBP is activated, promoting the transcription of genes involved in cholesterol synthesis and LDLR expression.

**In summary, cholesterol import is a multifaceted process that involves the uptake of cholesterol from the extracellular environment through both receptor-mediated and non-receptor-mediated mechanisms. This process is tightly regulated by cellular cholesterol levels and complex signaling pathways, ensuring that cells obtain the appropriate amount of cholesterol for their needs.**'
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Proteins (2)

Compounds (2)