Metabolic signals influence cell-fate decisions in Dictyostelium discoideum

Nutrient-sensing plays a crucial role in maintaining cellular energy and metabolic homeostasis. Perturbations in sensing pathways are associated with a wide variety of pathologies, especially metabolic diseases. Very little is understood about sensing fluctuations in nutrients and how this information is integrated into physiological and metabolic adaptation that could further affect cell-fate decisions during differentiation in Dictyostelium discoideum (henceafter, Dictyostelium). Glucose is the primary metabolic fuel among all nutrients. Carbohydrates, lipids and proteins ultimately breakdown into glucose, which is further used for providing energy. The maintenance of optimum glucose levels is important for efficient cell-survival. Glucose is not only a nutrient, but also a signaling molecule influencing cell growth and differentiation in Dictyostelium. Modulation of endogenous glucose levels either by varying exogenous glucose levels or genetic overexpression or deletion of genes involved in glucose signaling lead to changes in endogenous metabolite levels such as ADP/ATP ratio, NAD⁺ /NADH ratio, cAMP and ROS levels which further influence cell-fate decisions. Here, we show that AMPKα and Sir2D are components of glucose-signaling pathway in Dictyostelium which adjust cell metabolism interdependently in response to nutrient-status and promote cell-fate decisions.