Diploid cells of the budding yeast Saccharomyces cerevisiae starved for nit
rogen differentiate into a filamentous growth form. Poor carbon sources suc
h as starches can also stimulate filamentation, whereas haploid cells under
go a similar invasive growth response in rich medium. Previous work has dem
onstrated a role for various alcohols, by-products of amino acid metabolism
, in altering cellular morphology. We found that several alcohols, notably
isoamyl alcohol and 1-butanol, stimulate filamentous growth in haploid cell
s in which this differentiation is normally repressed. Butanol also induces
cell elongation and changes in budding pattern, leading to a pseudohyphal
morphology, even in liquid medium. The filamentous colony morphology and ce
ll elongation require elements of the pheromone-responsive MAPK cascade and
TEC1, whereas components of the nutrient-sensing machinery, such as MEP2 G
PA2, and GPR1, do not affect this phenomenon. A screen for 1-butanol-insens
itive mutants identified additional proteins that regulate polarized growth
(BUD8, BEM1, BEM4, and FIG1), mitochondrial function (MSM1, MRP21, and HMI
1), and a transcriptional regulator (CHD1). Furthermore, we have also found
that ethanol stimulates hyperfilamentation in diploid cells, again in a MA
PK-dependent manner. Together, these results suggest that yeast may sense a
combination of nutrient limitation and metabolic by-products to regulate d
ifferentiation.