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Related Experiment Videos

Hepatocytic autophagy.

P O Seglen1, P B Gordon, I Holen

  • 1Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo.

Biomedica Biochimica Acta
|January 1, 1991
PubMed
Summary
This summary is machine-generated.

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Autophagy, a cellular degradation process, is regulated by nutrients and hormones. Specific inhibition of autophagic-lysosomal fusion by asparagine reveals a novel organelle, the amphisome, linking autophagy and endocytosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy is a fundamental cellular process for degrading cytoplasmic components.
  • Autophagic sequestration rates are similar for various cytosolic enzymes, suggesting a non-selective bulk process.
  • Nutritional and hormonal factors significantly influence autophagy.

Purpose of the Study:

  • To investigate the regulatory mechanisms of autophagy, particularly the initial sequestration step.
  • To elucidate the role of specific amino acids, hormones, and signaling pathways in modulating autophagy.
  • To characterize the function of the amphisome, a potential intermediate organelle in autophagy and endocytosis.

Main Methods:

  • Ultrastructural analysis to observe autophagic processes.

Related Experiment Videos

  • Measurement of autophagic sequestration rates.
  • Pharmacological manipulation using amino acids (asparagine), hormones (insulin, glucagon), adrenergic agonists, and signaling modulators (cAMP analogs, phosphodiesterase inhibitors, okadaic acid).

    • Main Results:

    • Autophagic sequestration is inhibited by amino acids, potentiated by insulin, and antagonized by glucagon.
    • Epinephrine and alpha 1-adrenergic agonists inhibit autophagic sequestration.
    • cAMP and protein phosphorylation also inhibit autophagic sequestration.
    • Asparagine specifically blocks autophagic-lysosomal fusion, leading to accumulation of autophaged material in prelysosomal vacuoles.
    • This accumulation is accessible to endocytosed enzymes, identifying the amphisome.
    • Evidence suggests a ligand-dependent coupling of endocytosis and autophagy.

    Conclusions:

    • Autophagy regulation involves complex feedback mechanisms influenced by nutrients and hormones.
    • Asparagine's specific inhibition of autophagic-lysosomal fusion highlights the amphisome as a key organelle.
    • Amphisomes may serve as a crucial junction for integrating endocytic and autophagic pathways for lysosomal degradation.