Volatile anesthetics have been used in modern medicine for over 160 years, but their sites and mechanisms of action remain unclear. While many effects of these agents are characterized, how these effects relate to the physiological state of anesthesia has not been elucidated. Volatile anesthetics affect all cells and tissues tested, including mammalian, plant, bacterial, and yeast cells. In yeast, these drugs arrest cell division in a manner that parallels their actions in mammals. To gain further insight into the cellular activities of these compounds, genes were isolated that, when overexpressed or deleted from the genome, alter the response of Saccharomyces cerevisiae (budding yeast) to the volatile anesthetic isoflurane. One of the genes we identified is UMP1, which encodes a chaperone required for maturation of the 20S proteasome complex in yeast. Overexpression of UMP1 renders yeast cells more resistant to the growth inhibitory effects of isoflurane, while deletion of the gene renders cells more sensitive than wild type cells. This suggests an important role for the proteasome in responding to volatile anesthetics in yeast, and may provide clues as to how these drugs exert their effects in more complex eukaryotes, including mammals.
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