positive regulation of cholesterol storage

Definition

Target type: biologicalprocess

Any process that increases the rate or extent of cholesterol storage. Cholesterol storage is the accumulation and maintenance in cells or tissues of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. [GOC:BHF, GOC:dph, GOC:tb]

Positive regulation of cholesterol storage is a complex biological process that involves multiple cellular pathways and molecular mechanisms. It is essential for maintaining cholesterol homeostasis, which is crucial for the proper functioning of cell membranes, hormone synthesis, and other vital processes.

**Key players in positive regulation of cholesterol storage:**

* **Low-density lipoprotein (LDL) receptors:** These receptors on the cell surface bind to LDL particles in the bloodstream and mediate their uptake into cells. LDL particles are the primary carriers of cholesterol in the blood.
* **Sterol regulatory element-binding protein (SREBP):** This transcription factor plays a central role in regulating cholesterol synthesis and uptake. When cholesterol levels are low, SREBP is cleaved and translocated to the nucleus, where it activates genes involved in cholesterol synthesis and LDL receptor expression.
* **Acyl-CoA:cholesterol acyltransferase (ACAT):** This enzyme esterifies cholesterol, converting it into cholesteryl esters, which are stored in lipid droplets within cells. Cholesteryl esters are a more stable and less membrane-disruptive form of cholesterol.
* **Peroxisome proliferator-activated receptor alpha (PPARα):** This nuclear receptor is involved in lipid metabolism and can positively regulate cholesterol storage by activating genes involved in fatty acid oxidation and lipogenesis.
* **Other factors:** Hormones such as insulin and leptin, and factors like the availability of fatty acids and dietary cholesterol, can also influence cholesterol storage.

**Mechanism of positive regulation:**

1. **LDL uptake:** When LDL levels are high, LDL receptors on the cell surface bind to LDL particles and internalize them through endocytosis. This process delivers cholesterol into the cell.
2. **SREBP activation:** Low cholesterol levels activate SREBP, which translocates to the nucleus and activates genes involved in cholesterol synthesis (e.g., HMG-CoA reductase) and LDL receptor expression. This increases the synthesis of cholesterol and the uptake of LDL.
3. **Cholesterol esterification:** ACAT esterifies free cholesterol into cholesteryl esters, which are stored in lipid droplets. This process sequesters cholesterol, preventing it from accumulating in the cell membrane and disrupting its function.
4. **Regulation by other factors:** PPARα and hormones like insulin and leptin can also influence cholesterol storage by modulating the expression of genes involved in lipid metabolism and cholesterol uptake.

**Overall, positive regulation of cholesterol storage is a tightly regulated process that ensures adequate levels of cholesterol are available for essential cellular functions without causing harmful accumulation.**'
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Proteins (4)

Compounds (5)