[Abstract unavailable

Nutrient sensing and metabolic reprogramming are crucial for metazoan cell aging and tumor growth. Here, we identify metabolic and regulatory parallels between a layered, multicellular yeast colony and a tumor-affected organism. During development, a yeast colony stratifies into U and L cells occupying the upper and lower colony regions, respectively. U cells activate a unique metabolism controlled by the glutamine-induced TOR pathway, amino acid-sensing systems (SPS and Gcn4p) and signaling from mitochondria with lowered respiration. These systems jointly modulate U cell physiology, which adapts to nutrient limitations and utilize the nutrients released from L cells. Stress-resistant U cells share metabolic pathways and other similar characteristics with tumor cells, including the ability to proliferate. L cells behave similarly to stressed and starving cells, which activate degradative mechanisms to provide nutrients to U cells. Our data suggest a nutrient flow between both cell types, resembling the Cori cycle and glutamine-NH(4)(+) shuttle between tumor and healthy metazoan cells.

The existence of programmed cell death (PCD) in yeast and its significance to simple unicellular organisms is still questioned. However, such doubts usually do not reflect the fact that microorganisms in nature exist predominantly within structured, multicellular communities capable of differentiation, in which a profit of individual cells is subordinated to a profit of populations. In this study, we show that some PCD features naturally appear during the development of multicellular Saccharomyces cerevisiae colonies. An ammonia signal emitted by aging colonies triggers metabolic changes that localize yeast death only in the colony center. The remaining population can exploit the released nutrients and survives. In colonies defective in Sok2p transcription factor that are unable to produce ammonia (Váchová, L., F. Devaux, H. Kucerova, M. Ricicova, C. Jacq, and Z. Palková. 2004. J. Biol. Chem. 279:37973–37981), death is spread throughout the whole population, thus decreasing the lifetime of the colony. The absence of Mca1p metacaspase or Aif1p orthologue of mammalian apoptosis-inducing factor does not prevent regulated death in yeast colonies.

On solid substrate, growing yeast colonies alternately acidify and alkalinize the medium. Using morphological, cytochemical, genetic, and DNA microarray approaches, we characterized six temporal steps in the "acid-to-alkali" colony transition. This transition is connected with the production of volatile ammonia acting as starvation signal between colonies. We present evidence that the three membrane proteins Ato1p, Ato2p, and Ato3p, members of the YaaH family, are involved in ammonia production in Saccharomyces cerevisiae colonies. The acid-to-alkali transition is connected with decrease of mitochondrial oxidative catabolism and by peroxisome activation, which in parallel with activation of biosynthetic pathways contribute to decrease the general stress level in colonies. These metabolic features characterize a novel survival strategy used by yeast under starvation conditions prevalent in nature.

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