Bicarbonate‐mediated social communication stimulates meiosis and sporulation of Saccharomyces cerevisiae

Abstract

Meiosis and sporulation in the yeast Saccharomyces cerevisiae requires social communication, mediated by an extracellular factor which is secreted from cells during sporulation and accumulates in a cell density-dependent manner. We show here genetic and biochemical analyses supporting our conclusion that the extracellular factor is bicarbonate acting as an alkali to elevate extracellular pH. Sporulation defects of mdh1 (mitochondrial malate dehydrogenase) mutants and of wild-type cells at low density were rescued extracellularly by addition of bicarbonate or other alkaline solutions to raise medium pH. Addition of bicarbonate (or alkalization of medium) raised steady-state levels of mRNA in respiration-deficient mdh1 mutants and inhibited proliferation of wild-type cells at low density. These results indicate that the two conditions (respiration competency and high cell density), required for meiosis and sporulation, are essential for extracellular accumulation of bicarbonate and resulting alkalization of medium.

The Rim101p/PacC Pathway and Alkaline pH Regulate Pattern Formation in Yeast Colonies

“…This model is consistent with an earlier finding that cells in sporulation cultures secrete bicarbonate (an alkali), and this bicarbonate stimulates sporulation in these cultures (Ohkuni et al 1998). Bicarbonate is produced during sporulation as a result of respiratory metabolism of nonfermentable carbon sources, and it is likely that secretion of alkali is just one of several ways that respiration and nonfermentable carbon sources stimulate sporulation (Treinin and Simchen 1993;Jambhekar and Amon 2008).…”

“…Alkaline pH as both cause and effect of sporulation in colonies: As described in the Introduction, an alkaline pH environment has been implicated as both a by-product of sporulation and a signal that stimulates sporulation (Ohkuni et al 1998). Thus, alkaline pH is a candidate for a cell-to-cell signal that regulates sporula- tion in colonies.…”

“…Nonfermentable carbon sources stimulate sporulation directly, and metabolism of these carbon sources (via respiration) can also promote sporulation (Jambhekar and Amon 2008). Respiration causes an increase in the pH of the media as a result of cells secreting bicarbonate, and this increased pH may further stimulate sporulation in cultures (Ohkuni et al 1998). Activation of sporulation by alkaline pH might occur through the highly conserved Rim101/PacC pathway (Penalva and Arst 2004), since this pathway activates transcription of many genes that respond to alkaline pH, including genes required for sporulation (Lamb and Mitchell 2003;Rothfels et al 2005).…”

Sporulation in the Budding Yeast Saccharomyces cerevisiae

“…At higher or lower cell concentrations, sporulation efficiency drops off significantly. The basis for this dependence is that cells, prior to initiating sporulation, alkalinize the medium Ohkuni et al 1998). At optimal cell density, the pH of the medium reaches 7 to 8, whereas at lower or higher cell concentrations, the pH remains too acidic or becomes too alkaline.…”

Acetate Regulation of Spore Formation Is under the Control of the Ras/Cyclic AMP/Protein Kinase A Pathway and Carbon Dioxide in Saccharomyces cerevisiae

“…The glyoxylate and tricarboxylic acid (TCA) cycles metabolize acetate during sporulation; the main products are carbon dioxide, energy, as well as glutamate at early and trehalose at later stages of sporulation (12,13,34). In yeast cells, the carbonic anhydrase Nce103 catalyzes the reversible reaction of carbon dioxide and water to proton and bicarbonate (9,16), with the latter serving as a second messenger which enhances sporulation (19,20,42).…”