In mammals, O2 and CO2 levels are tightly regulated and are altered under various pathological conditions. While the molecular mechanisms that participate in O2 sensing are well characterized, little is known regarding the signaling pathways that participate in CO2 signaling and adaptation. Here, we show that CO2 levels control a distinct cellular transcriptional response that differs from mere pH changes. Unexpectedly, we discovered that CO2 regulates the expression of cholesterogenic genes in a SREBP2-dependent manner and modulates cellular cholesterol accumulation. Molecular dissection of the underlying mechanism suggests that CO2 triggers SREBP2 activation through changes in endoplasmic reticulum (ER) membrane cholesterol levels. Collectively, we propose that SREBP2 participates in CO2 signaling and that cellular cholesterol levels can be modulated by CO2 through SREBP2.

中文翻译：

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二氧化碳通过 SREBP2 调节胆固醇水平。

在哺乳动物中，O2 和 CO2 水平受到严格调节，并在各种病理条件下发生变化。虽然参与 O2 传感的分子机制已得到很好的表征，但对于参与 CO2 信号传导和适应的信号通路却知之甚少。在这里，我们表明 CO2 水平控制着不同于单纯 pH 变化的独特细胞转录反应。出乎意料的是，我们发现CO2以SREBP2依赖性方式调节胆固醇生成基因的表达并调节细胞胆固醇积累。对潜在机制的分子剖析表明，CO2 通过改变内质网 (ER) 膜胆固醇水平来触发 SREBP2 激活。总的来说，我们认为 SREBP2 参与 CO2 信号传导，并且 CO2 可通过 SREBP2 调节细胞胆固醇水平。