AMPK contributes to autophagosome maturation and lysosomal fusion View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-08-23

AUTHORS

Minsu Jang, Rackhyun Park, Hyunju Kim, Sim Namkoong, Daum Jo, Yang Hoon Huh, Ik-Soon Jang, Jin I. Lee, Junsoo Park

ABSTRACT

AMP-activated protein kinase (AMPK) regulates autophagy initiation when intracellular ATP level decreases. However, the role of AMPK during autophagosome maturation is not fully understood. Here, we report that AMPK contributes to efficient autophagosome maturation and lysosomal fusion. Using CRISPR-Cas9 gene editing, we generated AMPK α1 knockout HEK293T cell lines, in which starvation-induced autophagy is impaired. Compound C, an AMPK-independent autophagy inducer, and trehalose, an mTOR-independent autophagy inducer were used to examine the role of AMPK in autophagosome maturation and lysosomal fusion. While the treatment of control cells with either compound C or trehalose induces activation of autophagosomes as well as autolysosomes, the treatment of AMPK α1 knockout cells with compound C or trehalose induces mainly activation of autophagosomes, but not autolysosomes. We demonstrate that this effect is due to interference with the fusion of autophagosomes with lysosomes in AMPK α1 knockout cells. The transient expression of AMPK α1 can rescue autophagosome maturation. These results indicate that AMPK α1 is required for efficient autophagosome maturation and lysosomal fusion. More... »

PAGES

12637

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-30977-7

DOI

http://dx.doi.org/10.1038/s41598-018-30977-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106199581

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30140075


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