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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,...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
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...
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...

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Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase
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Cell-Based Drug Screening for Inhibitors of Autophagy Related 4B Cysteine Peptidase

Published on: June 30, 2023

Proteases in autophagy.

Vitaliy Kaminskyy1, Boris Zhivotovsky

  • 1Institute of Environmental Medicine, Division of Toxicology, Karolinska Instituet, Stockholm, Sweden.

Biochimica Et Biophysica Acta
|June 7, 2011
PubMed
Summary
This summary is machine-generated.

Proteases are crucial enzymes in autophagy, initiating and executing the process by degrading cellular components. However, some proteases can also inhibit autophagy, highlighting their complex regulatory roles.

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In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Autophagy is a fundamental cellular process for degrading macromolecules within lysosomes.
  • Proteases, enzymes that cleave peptide bonds, are critical for both initiating and executing autophagy.
  • Proteases can also play inhibitory roles in autophagy under specific conditions.

Purpose of the Study:

  • To review the multifaceted roles of proteases in the context of autophagy.
  • To elucidate how different protease families influence autophagic pathways.
  • To discuss the current understanding of protein degradation via autophagy and protease involvement.

Main Methods:

  • Literature review and synthesis of existing research on autophagy and proteases.
  • Analysis of the mechanisms by which specific proteases (e.g., Atg4, cathepsins, calpains, caspases) interact with autophagy-related proteins.
  • Discussion of experimental evidence supporting the dual role of proteases in promoting and inhibiting autophagy.

Main Results:

  • The cysteine protease Atg4 is essential for processing Atg8, a key step in macroautophagy initiation and autophagosome formation.
  • Lysosomal cathepsins (cysteine, serine, aspartic) degrade autophagosomal substrates and lysosomal components, influencing autophagic flux.
  • Certain proteases, like cathepsin A and caspases, can inhibit autophagy by cleaving regulatory proteins such as LAMP-2A.

Conclusions:

  • Proteases exhibit a complex regulatory role in autophagy, acting as both facilitators and inhibitors.
  • Understanding protease activity is vital for comprehending the complete autophagic process and its dysregulation.
  • This review highlights the critical interplay between proteolysis and autophagy, emphasizing the need for further research into these interactions.