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Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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,...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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Regulated Protein Degradation02:58

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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.
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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.
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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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TFEB regulates lysosomal proteostasis.

Wensi Song1, Fan Wang, Marzia Savini

  • 1Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, USA.

Human Molecular Genetics
|February 9, 2013
PubMed
Summary
This summary is machine-generated.

Transcription factor EB (TFEB) activation enhances protein folding and lysosomal activity, offering a potential therapeutic strategy for lysosomal storage disorders (LSDs) by rescuing destabilized enzyme variants.

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Multicolor Flow Cytometry-based Quantification of Mitochondria and Lysosomes in T Cells
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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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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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Multicolor Flow Cytometry-based Quantification of Mitochondria and Lysosomes in T Cells
06:22

Multicolor Flow Cytometry-based Quantification of Mitochondria and Lysosomes in T Cells

Published on: January 9, 2019

Area of Science:

  • Cellular Biology
  • Genetics
  • Biochemistry

Background:

  • Loss-of-function diseases, particularly lysosomal storage disorders (LSDs), often stem from mutations causing protein misfolding and degradation.
  • Current therapeutic strategies lack specific modulators for lysosomal proteostasis to correct these destabilizing mutations.

Purpose of the Study:

  • To investigate the role of transcription factor EB (TFEB) in modulating lysosomal proteostasis for treating LSDs.
  • To determine if TFEB activation can rescue the function of destabilized enzyme variants in LSDs.

Main Methods:

  • Investigated TFEB's role in lysosomal proteostasis using a glucocerebrosidase (GC) variant in Gaucher disease (GD) and a β-hexosaminidase mutant in Tay-Sachs disease.
  • Assessed the impact of TFEB activation on protein folding, trafficking, and enzyme activity.

Main Results:

  • TFEB activation enhanced folding, trafficking, and lysosomal activity of a destabilized GC variant in Gaucher disease.
  • TFEB induced expression of GC and genes involved in folding and lysosomal trafficking.
  • TFEB activation also rescued activity of a β-hexosaminidase mutant, suggesting broad applicability for LSDs.

Conclusions:

  • Transcription factor EB (TFEB) is identified as a specific regulator of lysosomal proteostasis.
  • TFEB activation presents a potential therapeutic target for rescuing enzyme homeostasis in lysosomal storage disorders.