Membrane fluidity and temperature sensing are coupled via circuitry comprised of Ole1, Rsp5, and Hsf1 in Candida albicans.
Membrane fluidity and temperature sensing are coupled via circuitry comprised of Ole1, Rsp5, and Hsf1 in Candida albicans.
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DOI：
10.1128/ec.00138-14
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Cowen LE
中科院分区：
文献类型：
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作者：
Leach MD;Cowen LE
温度是一个普遍存在的环境变量，它可以深刻地影响活细胞的生理，因为它随时间和空间的变化。当酵母细胞暴露于亚致死热休克时，正常的代谢功能被抑制，热休克转录因子Hsf1被激活，诱导热休克蛋白（HSP）。白色念珠菌是最普遍的人类真菌病原体，是一种机会致病菌，已进化为健康个体的相对无害的寄生虫。即使C.白色念珠菌占据热缓冲的小生境，它保留了经典的热休克反应，在缓慢的热转换过程中激活Hsf1，如发热患者所遭受的温度升高。然而，真菌病原体的温度传感机制仍然是个谜。对酿酒酵母的一些研究表明，热应激在膜水平上被转导为细胞信号。在这项研究中，我们操纵C。白色念珠菌膜来剖析温度感应机制。我们确定，响应于升高的温度，编码脂肪酸去饱和酶的OLE1水平降低。随后，OLE1的缺失触发编码脂肪酸合酶的FAS 2的表达。此外，OLE1的缺失阻止了Hsf1的完全激活，从而减少了热休克反应中HSP的表达。这种Hsf1激活的减少归因于E3泛素连接酶Rsp5，其调节OLE1表达。据我们所知，这是第一个确定脂肪酸合成和真菌王国热休克反应之间分子联系的研究。
Temperature is a ubiquitous environmental variable which can profoundly influence the physiology of living cells as it changes over time and space. When yeast cells are exposed to a sublethal heat shock, normal metabolic functions become repressed and the heat shock transcription factor Hsf1 is activated, inducing heat shock proteins (HSPs). Candida albicans, the most prevalent human fungal pathogen, is an opportunistic pathogen that has evolved as a relatively harmless commensal of healthy individuals. Even though C. albicans occupies thermally buffered niches, it has retained the classic heat shock response, activating Hsf1 during slow thermal transitions such as the increases in temperature suffered by febrile patients. However, the mechanism of temperature sensing in fungal pathogens remains enigmatic. A few studies with Saccharomyces cerevisiae suggest that thermal stress is transduced into a cellular signal at the level of the membrane. In this study, we manipulated the fluidity of C. albicans membrane to dissect mechanisms of temperature sensing. We determined that in response to elevated temperature, levels of OLE1, encoding a fatty acid desaturase, decrease. Subsequently, loss of OLE1 triggers expression of FAS2, encoding a fatty acid synthase. Furthermore, depletion of OLE1 prevents full activation of Hsf1, thereby reducing HSP expression in response to heat shock. This reduction in Hsf1 activation is attributable to the E3 ubiquitin ligase Rsp5, which regulates OLE1 expression. To our knowledge, this is the first study to define a molecular link between fatty acid synthesis and the heat shock response in the fungal kingdom.