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Papuamine prevents the fusion between autophagosomes and lysosomes by inhibiting the maturation of autophagosomes
Author(s) -
Fujimoto Keiko,
Tadakuma Ryo,
Tanaka Chiaki,
Hirota Yuko,
Miyauchi Yuu,
Ishii Yuji,
Tanaka Yoshitaka
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.661.1
Subject(s) - autophagy , lysosome , autophagosome , microbiology and biotechnology , endosome , bafilomycin , vesicle , chemistry , western blot , organelle , apoptosis , biology , intracellular , biochemistry , enzyme , membrane , gene
Papuamine, an alkaloid isolated from a marine sponge Haliclona sp., has been shown to have antifungal and antimycobacterial activities. Recent studies have reported that papuamine exhibits cytotoxicity and induces apoptosis in MCF7 breast cancer cells, which are attributable to the induction of autophagy. However, the effect of papuamine on autophagic flux remains uncertain. Therefore, the aim of this study was to investigate the effect of papuamine on autophagy. Western blot analyses showed that treatment of HeLa cells with papuamine causes a markedly increase in LC3‐II, an autophagosome‐specific marker. Likewise, confocal immunofluorescence microscopy revealed that not only the number of, but also the size of, LC3‐positive vesicles increased in papuamine‐treated cells. However, in cells treated with papuamine LC3‐positive vesicles were not significantly colocalized with a late endosome/lysosome marker LAMP‐1. In addition, papuamine did not affect lysosomal properties including acidic pH, activities and distribution of lysosomal enzymes. These results demonstrate that papuamine inhibits the fusion between autophagosomes and lysosomes, thereby leading to the accumulation of autophagosomes. Furthermore, our data suggest that papuamine‐induced impairment of both the autophagosomes‐lysosomes and the enlarged autophagosomes formation is due to a blockade of Rab5‐to‐Rab7 conversion. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .