Related Experiment Video

Updated: Nov 11, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
06:58

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

Published on: October 18, 2024

975

New functions of a known autophagy regulator: VCP and autophagy initiation

Yuchen Lei1, Daniel J Klionsky1

  • 1Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.

Autophagy
|March 31, 2021
PubMed

Insights

Valosin-containing protein (VCP) regulates autophagy initiation by stabilizing BECN1 and enhancing phosphoinositide 3-kinase (PtdIns3K) complex assembly, revealing a previously overlooked role in early autophagosome formation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • The protein VCP (Valosin-Containing Protein) is a conserved ATPase implicated in diverse cellular functions and linked to various human diseases.
  • VCP's role in autophagosome maturation is established, but its involvement in the earlier stages of autophagy, specifically autophagosome formation, remains less understood.

Discussion:

  • This study investigates the underappreciated role of VCP in the initiation phase of autophagy.
  • Utilizing small-molecule inhibitors, the research demonstrates VCP's critical function in the early steps of autophagosome biogenesis.

Key Insights:

  • VCP actively regulates autophagy initiation through two key mechanisms.
  • It stabilizes BECN1, a crucial protein in autophagy initiation.
  • It enhances the assembly of the phosphoinositide 3-kinase (PtdIns3K) complex, vital for autophagosome formation.

Outlook:

  • Further research into VCP's role in autophagy initiation could uncover new therapeutic targets for VCP-associated diseases.
  • Understanding VCP's precise molecular mechanisms in complex assembly offers avenues for targeted interventions.
  • This work highlights the importance of exploring less-obvious functions of proteins involved in fundamental cellular processes like autophagy.
Keywords:
ATXN3BECN1Ptdins3KVCPautophagy initiation

More Related Videos

Study of Protein-protein Interactions in Autophagy Research14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.3K
Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry11:39

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry

Published on: July 21, 2017

31.7K

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,...
5.2K
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...
3.7K
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...
8.4K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.0K
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.7K
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
4.3K