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首页> 外文期刊>Current Biology: CB >Transcriptional Regulation by Pho23 Modulates the Frequency of Autophagosome Formation
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Transcriptional Regulation by Pho23 Modulates the Frequency of Autophagosome Formation

机译：Pho23的转录调控调节自噬体形成的频率。

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Background: Autophagy as a conserved lysosomal/vacuolar degradation and recycling pathway is important in normal development and physiology, and defects in this process are linked to many kinds of disease. Because too much or too little autophagy can be detrimental, the process must be tightly regulated both temporally and in magnitude. Two parameters that affect this regulation are the size and the number of autophagosomes; however, although we know that the amount of Atg8 affects the size of autophagosomes, the mechanism for regulating their number has not been elucidated. The transcriptional induction and repression of the autophagy-related (ATG) genes is one crucial aspect of autophagy regulation, but the transcriptional regulators that modulate autophagy are not well characterized. Results: We detected increased expression levels of ATG genes, and elevated autophagy activity, in cells lacking the transcriptional regulator Pho23. Using transmission electron microscopy, we found that PHO23 null mutant cells contain significantly more autophagosomes than the wild-type. By RNA sequencing transcriptome profiling, we identified ATG9 as one of the key targets of Pho23, and our studies with strains expressing modulated levels of Atg9 show that the amount of this protein directly correlates with the frequency of autophagosome formation and the level of autophagy activity. Conclusions: Our results identified Pho23 as a master transcriptional repressor for autophagy that regulates the frequency of autophagosome formation through its negative regulation of ATG9.
机译：背景：自噬是一种保守的溶酶体/微泡降解和再循环途径，在正常的发育和生理学中很重要，该过程中的缺陷与多种疾病有关。由于过多的或过多的自噬可能是有害的，因此必须在时间和强度上严格控制该过程。影响该调控的两个参数是自噬体的大小和数量。然而，尽管我们知道Atg8的量会影响自噬体的大小，但尚未阐明调节其数目的机制。自噬相关（ATG）基因的转录诱导和抑制是自噬调控的一个关键方面，但调节自噬的转录调控因子并没有得到很好的表征。结果：我们在缺乏转录调节因子Pho23的细胞中检测到ATG基因表达水平增加，自噬活性升高。使用透射电子显微镜，我们发现PHO23空突变细胞比野生型包含更多的自噬体。通过RNA测序转录组分析，我们将ATG9鉴定为Pho23的关键靶标之一，我们对表达Atg9调节水平的菌株的研究表明，该蛋白的量与自噬体形成的频率和自噬活性的水平直接相关。结论：我们的结果确定Pho23是自噬的主要转录阻遏物，可通过其对ATG9的负调控来调节自噬体形成的频率。

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