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Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Lysosomes01:31

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Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
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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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Maturation of Endosomes01:28

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The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
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The Unfolded Protein Response01:37

The Unfolded Protein Response

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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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Export of Misfolded Proteins out of the ER01:32

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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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The Endo-Lysosomal Damage Response.

Hemmo Meyer1, Bojana Kravic1

  • 1Center of Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen, Germany;

Annual Review of Biochemistry
|April 10, 2024
PubMed
Summary

Cells possess a sophisticated response to lysosomal damage, involving repair, degradation via lysophagy, and regeneration of new lysosomes. This process is crucial for maintaining cellular health and fighting diseases.

Keywords:
autophagyendosomal sorting complexes required for transportlysophagylysosomal membrane permeabilizationlysosomesubiquitin

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cellular Homeostasis

Background:

  • Lysosomes are critical cellular organelles responsible for degradation.
  • Damage to lysosomes threatens cellular homeostasis and can trigger cell death and inflammation.
  • Cells have evolved a multi-pronged damage response to maintain lysosomal integrity.

Purpose of the Study:

  • To elucidate the cellular response mechanisms to endo-lysosomal damage.
  • To understand the interplay between lysosomal repair, degradation, and biogenesis.
  • To highlight the role of this response in disease and cancer.

Main Methods:

  • The abstract does not specify methods.
  • This section would typically detail experimental approaches used to study lysosomal damage and repair.
  • Potential methods include live-cell imaging, genetic manipulation, and biochemical assays.

Main Results:

  • Cells activate repair pathways to restore lysosomal membrane integrity.
  • If repair fails, damaged lysosomes undergo lysophagy (selective autophagy).
  • An mTORC1-dependent pathway promotes lysosome biogenesis and regeneration.

Conclusions:

  • The cellular response to lysosomal damage is essential for cellular health.
  • This response pathway is vital in combating neurodegeneration and infection.
  • Lysosomal damage response pathways represent a potential vulnerability in cancer cells.