The bidirectional relationship between metabolism and cell cycle Biology Diagrams The relationship between metabolism and cell cycle progression is complex and bidirectional. Cells must rewire metabolism to meet changing biosynthetic demands across cell cycle phases. In turn, metabolism can influence cell cycle progression through direct regulation of cell cycle proteins, through nutrient-sensing signaling pathways, and This altered metabolism fuels the growth and proliferation of cancer cells by providing energy and macromolecular building blocks, and it also contributes to the maintenance of redox balance (3, 4). A report in PNAS provides evidence for how glucose and glutamine metabolism are regulated during cell cycle progression. Proliferating cells must double each component of their mass over the course of the cell cycle to produce two daughter cells. Biosynthetic demands differ in each cell cycle phase [1,2]; therefore, metabolism must change in response to cell cycle progression. Cell cycle control must also be responsive to metabolic state to ensure that division only proceeds if cells can produce sufficient
We discuss how metabolism changes during different phases of the cell cycle to sustain biosynthesis and replication in normal and cancer cells. We also highlight how several master regulators of cell cycle, such as cyclin-cyclin-dependent kinases (cyc-CDK complexes) and E3 proteasome ligases, modulate key metabolic enzymes to support cell-cycle Cell cycle progression and division is regulated by checkpoint controls and sequential activation of cyclin-dependent kinases (CDKs). Understanding of how these events occur in synchrony with metabolic changes could have important therapeutic implications. For biosynthesis, cancer cells enhance glucose and glutamine consumption. Inactivation of pyruvate kinase M2 (PKM2) promotes transcription
The bidirectional relationship between metabolism and cell cycle ... Biology Diagrams
In conclusion, while incompletely understood, cell cycle progression is tightly coupled to intracellular metabolism. Emerging evidence suggests that intracellular kinases such as AMPK and mTOR can sense energy intermediates such as AMP, ADP and amino acids and subsequently direct how biosynthetic intermediates are used and whether the cell Regulation of cell proliferation by metabolism evolved in part to cope with nutritional deprivation, explaining why mechanisms arose to reduce cell growth and arrest cell cycle progression in conditions of starvation. 5 A key regulatory step early in the G 1 phase of the cell cycle is the growth factor-dependent restriction point, when cells
Uncovering cell cycle-associated metabolic processes is therefore of interest to find new avenues toward controlling cell proliferation. A number of observations suggest that some aspects of cellular metabolism are indeed coordinated with cell cycle progression.
