Cell Growth Regulation

Dear Colleagues,

Mammalian cells have developed a highly intricate network of signalling pathways that control their growth while maintaining energy and nutrient homeostasis. Mechanistic target of rapamycin (mTOR) lies at the heart of a cell growth signalling nexus that is lysosomally located, relaying upstream grow signals while also sensing the energy and nutrient status of the cell. Only when nutrients and energy are in sufficient supply can mTOR turn on anabolic processes to build cellular biomass. The capacity of a cell to grow is restricted by the supply of pre-cursor molecules necessary to generate proteins, lipids and DNA. Intracellular amino acid levels of the cell are increased through amino acid uptake and de novo biosynthesis and is necessary for growth. However, during states of starvation the cell needs to efficiently recycle amino acids to maintain their growth status. The proteasome and autophagy play an instrumental role in recycling amino acids and are tightly regulated by mTOR to maintain amino acid homeostasis. To rapidly build biomass in the growth phases of the cell cycle, mTOR has a multifaceted role, driving the efficiency of ribosomes to translate mRNA into protein while also manufacturing more of the ribosomal machinery through ribosomal biogenesis. Anabolic processes needed for cellular growth are highly energy demanding, so mTOR enhances mitochondrial biogenesis to generate more mitochondria, ensuring that the cell has enough capacity to generate energy as the cell grows. The ability of mTOR to switch between states of anabolic growth and catabolic fasting is dynamically regulated and is intrinsically coupled with the energy senor, AMPK. In the disease setting, improper mTOR signalling leads uncontrolled cell growth and homeostasis is lost. This review series will explore the range of mTOR-regulated processes that governs cell growth. We will review our current understanding of the complexities of mTOR and knowledge gaps in this topical research area.

Dr. Andrew R. Tee
Guest Editor

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