Hsp90 mediates the crosstalk between galactose metabolism and cell morphology pathways in yeast.

Galactose metabolism in the yeast Saccharomyces cerevisiae is carried out by a specialized GAL pathway consisting of structural and regulatory proteins. It is known that cells with unbalanced Gal proteins accumulate toxic metabolic intermediates and exhibit severe growth defects. Recently, we found that the molecular chaperone Hsp90 controls the abundance of multiple Gal proteins, possibly to prevent these defects. Hsp90 regulates various cellular processes including cell morphology in response to environmental cues. Yeast cells are known to resort to filamentous growth upon exposure to galactose or other environmental stresses. Our previous and current findings support the "Hsp90 titration model" of Hsp90 buffering, which links the cell morphology and galactose pathways. Our results suggest that, when a large proportion of Hsp90 molecules are used to help Gal proteins, the Hsp90 client proteins in cell morphology pathways are left unattended, leading to filamentous growth. It remains unclear whether this phenomenon serves any biological function or simply reflects a cellular constraint. Nonetheless, it provides an alternative explanation why the GAL pathway is degenerated in some yeast species.