Sulfur sequestration promotes multicellularity during nutrient limitation

The behaviour of Dictyostelium discoideum depends on nutrients(1). When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism(2,3). This biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species-generated as a consequence of nutrient limitation-lead to the sequestration of cysteine in the antioxidant glutathione. This sequestration limits the use of the sulfur atom of cysteine in processes that contribute to mitochondrial metabolism and cellular proliferation, such as protein translation and the activity of enzymes that contain an iron-sulfur cluster. The regulated sequestration of sulfur maintains D. discoideum in a nonproliferating state that paves the way for multicellular development. This mechanism of signalling through reactive oxygen species highlights oxygen and sulfur as simple signalling molecules that dictate cell fate in an early eukaryote, with implications for responses to nutrient fluctuations in multicellular eukaryotes.

Automated summary

The behavior of Dictyostelium discoideum is dependent on nutrients, existing as unicellular organisms in the presence of sufficient food and aggregating into multicellular organisms upon starvation. The generation of reactive oxygen species due to nutrient limitation leads to the sequestration of cysteine in the antioxidant glutathione, limiting its sulfur atom usage and maintaining the organism in a nonproliferating state conducive to multicellular development. This mechanism of signaling through reactive oxygen species highlights the roles of oxygen and sulfur as simple signaling molecules in dictating cell fate in early eukaryotes, with implications for responses to nutrient fluctuations in multicellular eukaryotes.