Mitochondria-nucleus energetic communication: Role for phosphotransfer networks in processing cellular information

Metabolic networks composed of the creatine kinase, adenylate kinase, and glycolytic phosphotransfer reactions are integral components of the cellular energetic infrastructure. Collectively, these pathways facilitate transfer and distribution of high-energy phosphoryls produced in the mitochondria through structured cytosolic and nuclear compartments. In this way, intracellular phosphotransfer relays secure efficient energetic and metabolic signaling, and thereby determining the fidelity of a range of cellular responses, including nucleocytoplasmic, metabolic, and genomic communications. The role and contribution of individual phosphotransfer enzymes depends on the species, tissue, developmental stage, or (patho) physiological state, underscoring the plasticity of the cellular energetic system in governing metabolic homeostasis. Catalyzed phosphotransfer along with related systems such as nucleoside diphosphate kinase (NDPK) play a vital role in organs with intense and fluctuating energy and signaling demands such as the heart or brain. Deletion of phosphotransfer enzyme isoforms compromises diverse cellular functions, including metabolic signaling, information processing, and adaptation of cellular energy metabolism to stress. Adaptive genetic reprogramming in conditions of phosphotransfer enzyme deficits is required to safeguard optimal cellular energetics. Emerging data indicate that coupling of phosphotransfer enzymes with metabolic sensors and phosphoryl-transferring protein kinase cascades comprises a unified intracellular energy/signal transduction matrix capable of processing, delivering, and retrieving cellular information. Here, recent evidence demonstrating the significance of compartmentalized and dynamically superimposed interactions of adenylate kinase, creatine kinase, and glycolytic enzyme-catalyzed phosphotransfers in orchestrating cytosolic and nuclear energetics is highlighted.