In Scarcity and Abundance: Metabolic Signals Regulating Cell Growth

摘要

Although nutrient availability is a major driver of cell growth, and continuous adaptation to nutrient supply is critical for the development and survival of all organisms, the molecular mechanisms of nutrient sensing are only beginning to emerge. Here, we highlight recent advances in the field of nutrient sensing and discuss arising principles governing how metabolism might regulate growth-promoting pathways. In addition, we discuss signaling functions of metabolic enzymes not directly related to their metabolic activity.Although first only recognized during tumor formation, it has become widely accepted that enhanced cell growth is generally associated with specific metabolic alterations, characterized by higher glycolytic flux and increased fermentation rates (production of lactate or ethanol). In cancers, this phenomenon is often referred to as the Warburg effect and is widely exploited for detection of tumors using PET scans, but it has also been identified as a promising new avenue for cancer treatment (3, 8, 132,136, 139). However, also in single cellular organisms such as yeast, in which cell growth is exclusively regulated by nutrient availability, increased cell growth is accompanied by reduced respiration dependence and higher glycolytic flux (37, 136). Yet, it is still rather unclear how these changes contribute to enhanced cell growth or whether the changes are mainly a consequence of cell growth.