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The Regulatory Proteins Rtg1/3 Govern Sphingolipid Homeostasis in the Human-Associated Yeast Candida albicans.
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-21 , DOI: 10.1016/j.celrep.2019.12.022 Sergio D Moreno-Velásquez 1 , Su Hlaing Tint 2 , Valentina Del Olmo Toledo 1 , Sanda Torsin 2 , Sonakshi De 2 , J Christian Pérez 1
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-21 , DOI: 10.1016/j.celrep.2019.12.022 Sergio D Moreno-Velásquez 1 , Su Hlaing Tint 2 , Valentina Del Olmo Toledo 1 , Sanda Torsin 2 , Sonakshi De 2 , J Christian Pérez 1
Affiliation
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Integrating nutrient sensing with the synthesis of complex molecules is a central feature of metabolism. Yet the regulatory mechanisms underlying such integration are often unknown. Here, we establish that the transcription regulators Rtg1/3 are key determinants of sphingolipid homeostasis in the human fungal pathogen Candida albicans. Quantitative analysis of the C. albicans lipidome reveals Rtg1/3-dependent alterations in all complex sphingolipids and their precursors, ceramides. Mutations in the regulators render the fungus susceptible to myriocin, a sphingolipid synthesis inhibitor. Rtg1/3 exert control on the expression of several enzymes involved in the synthesis of sphingolipids' building blocks, and the regulators are activated upon engulfment of C. albicans cells by human neutrophils. We demonstrate that Rtg1p and Rtg3p are regulated at two levels, one in response to sphingolipids and the other by the nutrient sensor TOR. Our findings, therefore, indicate that the Rtg1/3 system integrates nutrient sensing into the synthesis of complex lipids.
中文翻译：
调节蛋白Rtg1 / 3控制人类相关的酵母白色念珠菌中的鞘脂稳态。
将营养感测与复杂分子的合成相结合是新陈代谢的主要特征。然而，这种整合所基于的监管机制通常是未知的。在这里，我们确定转录调节因子Rtg1 / 3是人类真菌病原体白色念珠菌中鞘脂稳态的关键决定因素。对白色念珠菌脂质组的定量分析显示，在所有复杂的鞘脂及其前体神经酰胺中，Rtg1 / 3依赖的变化。调节剂中的突变使真菌易感肌磷脂（一种鞘脂合成抑制剂）。Rtg1 / 3对参与鞘脂合成的几种酶的表达施加控制，并且在人类嗜中性白细胞吞噬白色念珠菌细胞后激活调节剂。我们证明Rtg1p和Rtg3p被调节在两个水平，一个响应鞘脂，另一个由营养传感器TOR调节。因此，我们的发现表明，Rtg1 / 3系统将营养感应整合到了复杂脂质的合成中。
更新日期：2020-01-22
中文翻译：
调节蛋白Rtg1 / 3控制人类相关的酵母白色念珠菌中的鞘脂稳态。
将营养感测与复杂分子的合成相结合是新陈代谢的主要特征。然而，这种整合所基于的监管机制通常是未知的。在这里，我们确定转录调节因子Rtg1 / 3是人类真菌病原体白色念珠菌中鞘脂稳态的关键决定因素。对白色念珠菌脂质组的定量分析显示，在所有复杂的鞘脂及其前体神经酰胺中，Rtg1 / 3依赖的变化。调节剂中的突变使真菌易感肌磷脂（一种鞘脂合成抑制剂）。Rtg1 / 3对参与鞘脂合成的几种酶的表达施加控制，并且在人类嗜中性白细胞吞噬白色念珠菌细胞后激活调节剂。我们证明Rtg1p和Rtg3p被调节在两个水平，一个响应鞘脂，另一个由营养传感器TOR调节。因此，我们的发现表明，Rtg1 / 3系统将营养感应整合到了复杂脂质的合成中。
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