Katagiri Naohiro, Kuroda Takao, Kishimoto Hiroyuki, Hayashi Yuki, Kumazawa Takuya, Kimura Keiji
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba 305-8577, Japan.
Sci Rep. 2015 Mar 10;5:8903. doi: 10.1038/srep08903.
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.
多种细胞应激可激活自噬，自噬参与细胞质物质的溶酶体降解，以维持营养稳态并清除有害成分。在此，我们表明RNA聚合酶I（Pol I）转录抑制会诱导核仁破坏和自噬。用自噬抑制剂或针对自噬相关（ATG）蛋白的小干扰RNA（siRNA）处理可抑制自噬，但不能抑制Pol I转录抑制诱导的核仁破坏，这表明核仁破坏位于自噬上游。此外，用针对核仁蛋白核磷蛋白（NPM）的siRNA处理可抑制此类自噬。这表明当核仁被Pol I抑制破坏时，NPM参与自噬。相比之下，营养饥饿诱导的经典自噬不需要NPM，因为它不伴有核仁破坏。因此，我们的结果表明，除了经典自噬外，可能还存在与核仁破坏相关的NPM依赖性自噬。
