Membrane Fluidity and Temperature Sensing Are Coupled via Circuitry Comprised of Ole1, Rsp5, and Hsf1 in Candida albicans

Temperature is a ubiquitous environmental variablewhich 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, normalmetabolic functions become repressed and the heat shock transcription factorHsf1 is activated, inducing heat shock proteins (HSPs).Candida albicans, the most prevalent human fun-gal pathogen, is an opportunistic pathogen that has evolved as a relatively harmless commensal of healthy individuals. Even thoughC. albicans occupies thermally buffered niches, it has retained the classic heat shock response, activatingHsf1 during slow thermal transitions such as the increases in temperature suffered by febrile patients.However, themechanismof 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. albicansmembrane to dissect mecha-nisms of temperature sensing. We determined that in response to elevated temperature, levels ofOLE1, encoding a fatty acid de-saturase, decrease. Subsequently, loss ofOLE1 triggers expression of FAS2, encoding a fatty acid synthase. Furthermore, deple-tion ofOLE1 prevents full activation of Hsf1, thereby reducingHSP expression in response to heat shock. This reduction in Hsf1 activation is attributable to the E3 ubiquitin ligase Rsp5, which regulatesOLE1 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. Microorganisms inhabit dynamic environments in which theyare continually exposed to environmental stimuli and stresses. Survival depends upon effective environmental respons