Cited by 1,312Autophagy in Disease and TherapyCellular transport and secretionATP Synthase and ATPases Research

Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells

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Yamamoto, Akitsugu, Tagawa, Yoshihiro, Yoshimori, Tamotsu, Moriyama, Yoshinori, Masaki, Ryuichi, Tashiro, Yutaka·1998·Cell Structure and Function

Abstract

We studied the effects of bafilomycin A1, a potent and specific inhibitor of vacuolar H+ ATPase (V-ATPase), on the process of autophagy in rat hepatoma cell line, H-4-II-E cells. To induce autophagy, cells were transferred from Dulbecco's modified Eagle medium containing 12% fetal calf serum into Hanks' balanced salt solution. When bafilomycin A1 was added to Hanks' balanced salt solution, endogenous protein degradation was strongly inhibited and numerous autophagosomes accumulated in H-4-II-E cells, whereas autolysosomes decreased in number. Acid phosphatase activity was not detected in the autophagosomes which accumulated in the presence of bafilomycin A1, suggesting that fusion between autophagosomes and lysosomes was disturbed by this drug. Inhibition of the fusion was reversible, and the autophagosomes changed into autolysosomes after the removal of the inhibitor. Bafilomycin A1 also prevented the appearance of endocytosed HRP in autophagic vacuoles. These results suggested that acidification of the lumenal space of autophagosomes or lysosomes by V-ATPase is important for the fusion between autophagosomes and lysosomes.

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  1. Bowman, E.M., Siebers, A., and Altendorf, K. 1988. Bafilo- mycins: A class of inhibitors of membraneATPase from micro- organisms, animal cells, and plant cells. Proc. NatI. Acad. Sci.
  2. Presley, J.F., Mayor, S., McGraw, T.E., Dunn, K.W., and Maxfield, F.R. 1997. Bafilomycin A2 treatment retards transfer- rin receptor recycling more than bulk membranerecycling. /. Biol. Chem., 272: 13929-13936.

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Authors
Yamamoto, A., Tagawa, Y., Yoshimori, T., Moriyama, Y., Masaki, R., & Tashiro, Y.
Affiliations
  • Kansai Medical University (JP)
  • National Institute for Basic Biology (JP)
  • The Institute of Scientific and Industrial Research, The University of Osaka (JP)
Venue
Cell Structure and Function
Published
1998
Volume
23
Issue
1
Pages
33-42
ISSN
  • 0386-7196 (ISSN-L)
  • 1347-3700
OpenAlex
W2077731318
Cited by
1,312
References
41
Citations by year
2026: 33 · 2025: 49 · 2024: 32 · 2023: 50 · 2022: 58 · 2021: 80 · 2020: 71 · 2019: 99 · 2018: 62 · 2017: 80 · 2016: 97 · 2015: 97 · 2014: 99 · 2013: 90 · 2012: 69
FWCI
3.47
Type
journal article
Language
en
Open access
Locations
  • Cell Structure and Function (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
bafilomycin A1, autophagy, autophagosome-lysosome fusion, autolysosomes, lysosomal acidification, hepatoma cells, acid phosphatase activity
MeSH terms
Amino Acids, Animals, Anti-Bacterial Agents, Autophagy, Cell Differentiation, Growth Inhibitors, Carcinoma, Hepatocellular, Histocytochemistry, Hydrogen-Ion Concentration, Kinetics, Lysosomes, Neoplasm Proteins, Phagosomes, Tumor Cells, Cultured, Vacuoles, Culture Media, Serum-Free, Culture Media, Conditioned, Macrolides, Rats

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