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Autophagosome–lysosome fusion is facilitated by plectin-stabilized actin and keratin 8 during macroautophagic process

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Abstract

Autophagy is a lysosome-mediated degradative process that removes damaged proteins and organelles, during which autophagosome–lysosome fusion is a key step of the autophagic flux. Based on our observation that intermediate cytofilament keratin 8 (KRT8) enhances autophagic clearance in cells under oxidative stress condition, we investigated whether KRT8 supports the cytoplasmic architectural networks to facilitate the vesicular fusion entailing trafficking onto filamentous tracks. We found that KRT8 interacts with actin filaments via the cytolinker, plectin (PLEC) during trafficking of autophagosome. When PLEC was knocked down or KRT8 structure was collapsed by phosphorylation, autophagosome–lysosome fusion was attenuated. Inhibition of actin polymerization resulted in accumulation of autophagosomes owing to a decrease in autophagosome and lysosome fusion. Furthermore, myosin motor protein was found to be responsible for vesicular trafficking along the actin filaments to entail autolysosome formation. Thus, the autophagosome–lysosome fusion is aided by PLEC-stabilized actin filaments as well as intermediate cytofilament KRT8 that supports the structural integrity of actin filaments during macroautophagic process under oxidative stress condition.

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This research was supported by the grant from the National Research Foundation of Korea (2017R1E1A1A01074656) funded by the Korean government.

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D-EK and AB formulated the hypothesis, and initiated and organized the study. SS and AB designed and performed experiments with data analysis. SS, AB, JHL and D-EK wrote the manuscript.

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Correspondence to Dong-Eun Kim.

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Son, S., Baek, A., Lee, J.H. et al. Autophagosome–lysosome fusion is facilitated by plectin-stabilized actin and keratin 8 during macroautophagic process. Cell. Mol. Life Sci. 79, 95 (2022). https://doi.org/10.1007/s00018-022-04144-1

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