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Megalomicin disrupts lysosomal functions

P Bonay1, M Fresno, B Alarcón

  • 1Centro de Biologia Molecular Severo Ochoa, CSIC-Universidad Autonoma de Madrid, Cantoblanco, Spain.

Journal of Cell Science
|August 1, 1997
PubMed

Insights

Megalomicin (MGM) rapidly swells lysosomes and blocks protein degradation. This drug impairs lysosome delivery and acidification, impacting cellular waste removal and antigen processing.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Megalomicin (MGM) disrupts Golgi complex morphology and inhibits protein transport.
  • This leads to accumulation of poorly sialylated glycoproteins.

Purpose of the Study:

  • To investigate the effects of MGM on lysosomal function and protein degradation.
  • To elucidate the mechanism behind MGM's cellular impact.

Main Methods:

  • Treatment of cultured cells with MGM.
  • Analysis of lysosomal swelling and degradation of T cell antigen receptor CD36 subunit.
  • Tracking fluid phase markers and endocytosed ovalbumin using Percoll density gradients.
  • Assessing epidermal growth factor receptor delivery to lysosomes.
  • In vitro assay of ATP-dependent lysosomal acidification.

Main Results:

  • MGM caused rapid lysosomal swelling and inhibited degradation of newly synthesized CD36.
  • MGM prevented degradation of fluid phase markers, which accumulated in endosomal fractions.
  • Delivery of membrane-bound epidermal growth factor receptor to lysosomes was also inhibited.
  • MGM strongly inhibited ATP-dependent lysosomal acidification in vitro.

Conclusions:

  • MGM impairs lysosomal function by inhibiting the delivery of endocytosed materials.
  • MGM disrupts lysosomal acidification, potentially explaining its in vivo effects.
  • MGM affects both soluble and membrane-bound protein degradation pathways within lysosomes.

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