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.
Highlights
Various cellular stresses activate autophagy, which is involved in lysosomal degradation of cytoplasmic materials for maintaining nutrient homeostasis and eliminating harmful components
A recent study revealed that the nucleolus, the nuclear component considered to be the site of RNA polymerase I (Pol I)-dependent ribosomal RNA synthesis and a ‘ribosome factory,’ acts as a stress sensor[9,10,11,12,13]
ADR treatment induced the conversion of light chain 3B (LC3B)-I to LC3B-II (Fig. 1b) and reduced p62 protein levels (Fig. 1b), both of which are indicators of autophagy. These results show that ADR treatment induced both nucleolar disruption and autophagy
Summary
Various cellular stresses activate autophagy, which is involved in lysosomal degradation of cytoplasmic materials for maintaining nutrient homeostasis and eliminating harmful components. The studies described below reveal that autophagy is induced by other types of stress, such as hypoxia, UV irradiation, chemical compounds and heat shock[1,3,5] Under these conditions, cells adapt to the stress by activating autophagy to eliminate damaged proteins and organelles[1,3,5]. A number of external and internal insults induce nucleolar stress by disrupting nucleolar structure, which leads to translocation of several nucleolar proteins from the nucleolus to the nucleoplasm, such as nucleophosmin (NPM; called B23) and nucleostemin and ribosomal proteins, such as RPS7, RPL5, RPL11 and RPL2311,14,15 These translocated proteins cause accumulation and activation of tumour suppressor p53 by interacting with the p53 inhibitor HDM2 and inhibiting HDM2 activity directed towards p5311,14,15. It is speculated that altered nucleolar structure may be related to inducing autophagy
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