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Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
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...

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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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Cholesterol depletion induces autophagy.

Jinglei Cheng1, Yuki Ohsaki, Kumi Tauchi-Sato

  • 1Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

Biochemical and Biophysical Research Communications
|October 24, 2006
PubMed
Summary

Cholesterol depletion activates macroautophagy, a cellular digestion process. This process, crucial for cell health, is triggered by reduced cholesterol levels via a phosphatidylinositol 3-kinase-dependent pathway.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy is a fundamental cellular process for degrading damaged components.
  • The precise molecular regulators of autophagy remain incompletely understood.
  • Cholesterol's role in regulating cellular processes is significant but not fully elucidated.

Purpose of the Study:

  • To investigate the effect of cellular cholesterol depletion on macroautophagy.
  • To identify the molecular mechanisms underlying cholesterol-mediated autophagy induction.

Main Methods:

  • Acute cholesterol depletion using methyl-beta-cyclodextrin or nystatin.
  • Metabolic cholesterol depletion using mevastatin and mevalonolactone.
  • Analysis of LC3-II levels via immunoblotting and immunofluorescence microscopy.
  • Assessment of autophagic vacuoles using electron microscopy.
  • Inhibition studies using phosphatidylinositol 3-kinase inhibitors.

Main Results:

  • Cholesterol depletion significantly induced macroautophagy in human fibroblasts, exceeding the effect of amino acid starvation.
  • LC3-II levels increased markedly, and autophagic vacuoles, often as long tubules, were observed.
  • The induction of autophagy by cholesterol depletion was dependent on phosphatidylinositol 3-kinase.
  • Cholesterol depletion led to the dephosphorylation of mammalian target of rapamycin.

Conclusions:

  • Decreased cellular cholesterol levels activate macroautophagy.
  • This activation occurs through a phosphatidylinositol 3-kinase-dependent signaling pathway.
  • The findings reveal a novel regulatory mechanism linking cholesterol homeostasis to autophagy.