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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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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.
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Cellular Injury V: Apoptosis and Autophagy01:22

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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...
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The Extrinsic Apoptotic Pathway01:17

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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mTOR Signaling and Cancer Progression03:03

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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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Related Experiment Video

Updated: May 4, 2026

The Lactate Dehydrogenase Sequestration Assay &#8212; A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells
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The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells

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A small switch has a large effect on autophagy.

Winfried Weissenhorn1, Marie-Odile Fauvarque2

  • 1University Grenoble Alpes, 38000 Grenoble, France; CNRS, UVHCI, 38000 Grenoble, France; Unit of Virus Host-Cell Interactions, University Grenoble Alpes-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.

Structure (London, England : 1993)
|January 14, 2014
PubMed
Summary
This summary is machine-generated.

Autophagy regulators, Atg8 family proteins and Atg13, were studied. Crystal structures reveal a side chain switch in light chain 3 (LC3) that controls its interaction with Atg13, impacting autophagosome formation.

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Related Experiment Videos

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

  • Molecular Biology
  • Cell Biology
  • Structural Biology

Background:

  • Autophagy is a crucial cellular process for degrading and recycling damaged components.
  • Atg8 family proteins and Atg13 are key regulators of autophagosome formation, the hallmark of autophagy.
  • Understanding the molecular mechanisms governing these interactions is vital for comprehending cellular homeostasis.

Purpose of the Study:

  • To elucidate the structural basis of the interaction between Atg8 family proteins, specifically light chain 3 (LC3), and the Atg13 protein.
  • To identify the molecular determinants that regulate the LC3-Atg13 interaction and its role in autophagosome biogenesis.

Main Methods:

  • X-ray crystallography was employed to determine the high-resolution structures of LC3 in complex with the Atg13 LC3-interacting region (LIR) motif.
  • In vivo experiments were conducted to assess the functional consequences of the identified structural switch on autophagosome formation.

Main Results:

  • Crystal structures revealed the atomic details of the LC3-LIR complex, highlighting a specific side chain conformation in LC3.
  • A subtle conformational switch in the LC3 side chain was identified as a critical regulator of the LC3-Atg13 interaction.
  • This conformational switch was demonstrated to be essential for efficient autophagosome formation in vivo.

Conclusions:

  • The study provides a detailed structural understanding of the LC3-Atg13 interaction, crucial for autophagy.
  • A novel regulatory mechanism involving a side chain conformational switch in LC3 controlling autophagosome formation has been uncovered.
  • These findings offer insights into the precise molecular control of autophagy initiation and progression.