The nucleolar protein nucleophosmin is essential for autophagy induced by inhibiting Pol I transcription

Scientific Reports
Naohiro KatagiriKeiji Kimura

Abstract

Various cellular stresses activate autophagy, which is involved in lysosomal degradation of cytoplasmic materials for maintaining nutrient homeostasis and eliminating harmful components. Here, we show that RNA polymerase I (Pol I) transcription inhibition induces nucleolar disruption and autophagy. Treatment with autophagy inhibitors or siRNA specific for autophagy-related (ATG) proteins inhibited autophagy but not nucleolar disruption induced by Pol I transcription inhibition, which suggested that nucleolar disruption was upstream of autophagy. Furthermore, treatment with siRNA specific for nucleolar protein nucleophosmin (NPM) inhibited this type of autophagy. This showed that NPM was involved in autophagy when the nucleolus was disrupted by Pol I inhibition. In contrast, NPM was not required for canonical autophagy induced by nutrient starvation, as it was not accompanied by nucleolar disruption. Thus, our results revealed that, in addition to canonical autophagy, there may be NPM-dependent autophagy associated with nucleolar disruption.

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Citations

Aug 26, 2018·Journal of Neurochemistry·Michal Hetman, Lukasz P Slomnicki
Jan 30, 2019·Pharmacogenetics and Genomics·Jong-Uk LeeJong-Sook Park
May 23, 2019·Frontiers in Cellular Neuroscience·Astrid S Pfister
Aug 17, 2019·Cells·David P DannheisigAstrid S Pfister
Oct 7, 2020·International Journal of Molecular Sciences·Annalisa PecoraroAnnapina Russo

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Methods Mentioned

BETA
transmission electron microscopy
electron microscopy
transfection
transgenic

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