Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition
Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition
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DOI：
10.1002/1873-3468.12195
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发表时间：
2016-06-01
期刊：
影响因子：
3.5
通讯作者：
Iwata, Hidehisa
中科院分区：
文献类型：
--
作者：
Sano, Osamu;Kazetani, Kenichi;Iwata, Hidehisa
溶酶体蛋白通过自噬降解，严格调节细胞蛋白的稳态。在这里，我们进行了高含量的筛选，以确定抑制自噬途径的化合物。我们得到了11个HIT化合物，并利用细胞形态信息进行了聚类分析。Vacuolin-1，它诱导形成巨大的空泡，是一个目标未知的化合物，与已知的PIKfyve抑制剂YM201636聚集在一起。我们进一步证实了液泡素-1是一种有效的PIKfyve抑制剂，并最终得出结论，PIKfyve抑制剂是一种新的调节自噬的化学工具。
Lysosomal protein degradation via autophagy strictly regulates cellular protein homoeostasis. Herein we performed high-content screening to identify compounds that inhibit autophagy pathways. We obtained 11 hit compounds and performed cluster analysis using cellular morphological information. Vacuolin-1, which induces the formation of giant vacuoles and is a target unknown compound, clustered with the known PIKfyve inhibitor YM201636. We further confirmed that vacuolin-1 is a potent PIKfyve inhibitor, and we finally concluded that PIKfyve inhibitors are novel chemical tools for regulating autophagy.