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Related Concept Videos

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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Updated: May 23, 2025

Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics
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Getting PIKy with the lysosome membrane (again).

Alison D Klein1,2, Michael Overholtzer1,2,3

  • 1BCMB Graduate Program, Weill Cornell Medical College, New York, NY, USA.

Autophagy Reports
|May 21, 2025
PubMed
Summary
This summary is machine-generated.

This study reveals PIKfyve kinase regulates microautophagy, a cellular process for degrading proteins. Stressors trigger this process, involving ATG8 proteins and PIKfyve, coordinating protein turnover with lysosome biogenesis.

Keywords:
ATG8CASMLC3PIKfyveTFEBTRPML1autophagylysosomemicroautophagy

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Microautophagy regulation remains largely unknown.
  • Lysosomal stress, induced by agents altering pH and osmotic potential, triggers selective transmembrane protein degradation via microautophagy.
  • This process involves the lysosomal targeting of macroautophagy proteins (ATG8s) through the CASM pathway.

Purpose of the Study:

  • To investigate the role of the lipid kinase PIKfyve in CASM-induced microautophagy.
  • To elucidate the relationship between PIKfyve, ATG8 proteins, and lysosome biogenesis transcription factor TFEB during lysosomal stress.

Main Methods:

  • Cellular treatment with lysomotropic drugs and proton ionophores.
  • Analysis of protein turnover, specifically ATG8s and lysosomal membrane proteins.
  • Investigating the dependency on PIKfyve activity and ATG8 lipidation.
  • Assessing TFEB induction in relation to CASM and PIKfyve.

Main Results:

  • CASM-induced microautophagy selectively degrades ATG8s and other lysosomal membrane proteins.
  • PIKfyve activity is required downstream of ATG8 lipidation for this turnover.
  • Lysosome biogenesis transcription factor TFEB is induced in parallel, dependent on CASM but independent of PIKfyve.

Conclusions:

  • Stressors activating CASM induce selective microautophagy for protein turnover.
  • This process is coordinated with lysosome biogenesis via a PIKfyve-dependent and independent mechanism.
  • PIKfyve acts as a key regulator downstream of ATG8 lipidation in CASM-induced microautophagy.