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

Michelle D. Leach, Leah E. Cowen

Research output: Contribution to journalArticle

29 Citations (Scopus)
5 Downloads (Pure)

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 sub lethal 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. Few studies in S. cerevisiae suggest that thermal stress is transduced into a cellular signal at the level of the membrane. In this study, we manipulate the fluidity of C. albicans membrane to dissect mechanisms of temperature sensing. We determined that in response to elevated temperature, levels of the fatty acid desaturase OLE1 decrease. Subsequently, loss of Ole1 triggers expression of the fatty acid synthase FAS2. 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.
Original languageEnglish
Pages (from-to)1077-1084
Number of pages8
JournalEukaryotic Cell
Volume13
Issue number8
Early online date20 Jun 2014
DOIs
Publication statusPublished - Aug 2014

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