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Related Concept Videos

Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

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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.
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Overview of Secretory Vesicles01:33

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Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
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Autophagy01:27

Autophagy

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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.
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Cholesterol: Significance and Regulation01:29

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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.
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Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

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Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
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Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

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After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
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Related Experiment Video

Updated: Jan 17, 2026

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
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Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

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Cholesterol Deficiency Directs Autophagy-Dependent Secretion of Extracellular Vesicles.

Jazmine D W Yaeger1, Sonali Sengupta1, Austin L Walz2

  • 1Cellular Therapies and Stem Cell Biology Group, Sanford Research, Sioux Falls, South Dakota, USA.

Journal of Extracellular Vesicles
|January 15, 2026
PubMed
Summary

Cholesterol depletion triggers increased release of extracellular vesicles (EVs) through an autophagy-dependent pathway. This finding reveals a novel mechanism linking cholesterol imbalance to EV secretion with potential disease implications.

Keywords:
Smith–Lemli–Opitzcancercholesterolexosomeextracellular vesicle

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Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Extracellular vesicle (EV) secretion is a key intercellular communication mechanism.
  • Lipid metabolism influences EV activity, but specific lipid impacts remain unclear.
  • Cholesterol's role in EV biogenesis and release is not well understood.

Purpose of the Study:

  • To investigate the impact of cholesterol biosynthesis disorders on extracellular vesicle (EV) secretion.
  • To elucidate the molecular mechanisms linking cholesterol levels to EV release.
  • To explore the pathological relevance of cholesterol-induced EV secretion.

Main Methods:

  • Analysis of small EVs (sEVs) from genetic and chemically induced cholesterol-depleted cells.
  • Transmission electron microscopy (TEM) to examine cellular ultrastructure.
  • CRISPR-mediated gene editing to inhibit autophagosome formation.
  • Validation in head and neck cancer cell models.

Main Results:

  • Cholesterol depletion, via genetic or synthetic inhibition, significantly increased sEV release.
  • sEVs from cholesterol-depleted cells exhibited structural deficits and altered surface markers but enhanced internalization.
  • Impaired cholesterol biosynthesis led to autophagic defects, with autophagosomes redirected to late endosomes.
  • Cholesterol depletion-induced sEV release was confirmed to be autophagy-dependent.

Conclusions:

  • Cholesterol imbalance initiates an autophagy-dependent pathway for sEV secretion.
  • Altered cholesterol metabolism impacts EV structure, function, and release.
  • This mechanism may be relevant in diseases characterized by cholesterol dysregulation.