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Related Concept Videos

Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Lipids: Dietary Sources and Requirements01:18

Lipids: Dietary Sources and Requirements

Lipids are an essential component of a balanced human diet. Triglycerides, which make up the majority of dietary lipids, are found in both saturated fats—commonly present in meat, dairy products, and certain tropical plants like coconut, and hydrogenated oils such as margarine and baking shortenings (trans fats)—and unsaturated fats, which are abundant in seeds, nuts, olive oil, and most vegetable oils. The main sources of cholesterol include egg yolks, various meats and organ meats, shellfish,...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Lipid Absorption01:24

Lipid Absorption

Dietary triglycerides from chyme in the duodenum are mixed with bile salts produced by the liver to emulsify fats. As a result, large droplets are broken down into smaller ones, increasing the surface area for enzymatic action. Once emulsified, pancreatic lipases hydrolyze the triglycerides into free fatty acids and monoglycerides.
These breakdown products bind with bile salts and lecithin to form micelles, which quickly pass between microvilli to come in close contact with the apical...

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Related Experiment Video

Updated: Jun 26, 2026

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover.

Xue Feng1, Shuo Zhang2, Yuqi Wang2

  • 1Department of Medicine, University of California, San Diego, San Diego, CA, USA. x5feng@health.ucsd.edu.

Nature
|June 24, 2026
PubMed
Summary
This summary is machine-generated.

A newly discovered Ral GTPase pathway controls hepatic low-density lipoprotein receptor (LDLR) levels, crucial for cholesterol balance. This pathway degrades LDLR in lysosomes, offering a new target for treating high cholesterol.

More Related Videos

Cholesterol Efflux Assay
07:54

Cholesterol Efflux Assay

Published on: March 6, 2012

Related Experiment Videos

Last Updated: Jun 26, 2026

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

Cholesterol Efflux Assay
07:54

Cholesterol Efflux Assay

Published on: March 6, 2012

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatic low-density lipoprotein receptor (LDLR) metabolism is vital for cholesterol homeostasis.
  • Molecular mechanisms coordinating LDLR trafficking and turnover in response to dietary cholesterol are not fully understood.

Purpose of the Study:

  • To identify molecular pathways linking dietary cholesterol signals to LDLR turnover.
  • To elucidate the role of Ral GTPases in regulating LDLR metabolism.

Main Methods:

  • Investigated Ral GTPase activation by dietary cholesterol in hepatocytes.
  • Utilized genetic manipulation (RalGAPB deletion, active Ral mutants) and biochemical assays.
  • Examined LDLR trafficking, lysosomal degradation, and cathepsin A (CTSA) activity.

Main Results:

  • Chronic dietary cholesterol activates Ral GTPases, promoting LDLR lysosomal degradation and inhibiting recycling.
  • Ral activation routes LDLR via the RalBP1-REPS1 complex for internalization and lysosomal degradation by CTSA.
  • Ral pathway activation enhances lysosomal CTSA maturation and limits its secretion, increasing LDLR breakdown.

Conclusions:

  • A novel Ral GTPase pathway regulates hepatic LDLR turnover independently of transcriptional control or PCSK9.
  • Genetic variants in this pathway correlate with human cholesterol levels.
  • CTSA inhibition presents a potential therapeutic strategy for hypercholesterolaemia by enhancing LDLR function and cholesterol clearance.