Cowen, Leah E.

Leach, Michelle D.

Eukaryotic Cell

English

PubMed

The Open University

Membrane fluidity and temperature sensing are coupled via circuitry comprised of Ole1, Rsp5, and Hsf1 in Candida albicans

ABSTRACT
          
            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.
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Michelle D. Leach

Leah E. Cowen

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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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The Open University

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