TOR signalling

Dai and colleagues show that activation of AMPK by glucose starvation leads to phosphorylation of GATOR2 and affects nutrient-dependent activation of mTORC1.

mTORC1 integrates environmental signals to promote anabolism and repress catabolism. In this issue of Nature Metabolism, Hosios et al. identify a role for mTORC1 in controlling endosomal trafficking and degradation of membrane phospholipids in the lysosome, revealing a novel process used by cells to adapt to poor growth conditions.

The Rag GTPases form the link between extracellular nutrients and the activation of mTORC1. RagA/B and RagC/D have been considered functionally redundant, but two studies now show that each isoform and gene have specific features, making their control of mTORC1 activity more nuanced and complex than previously appreciated.

Ong et al. uncover a role for the YAP/TAZ–TEAD transcriptional pathways in retinal angiogenesis via the regulation of amino acid transporters and assessed mTORC activation. These findings establish the mechanism through which endothelial cells regulate nutrient acquisition and consumption.

Nutrient availability and the cell cycle are known to affect chromatin accessibility. A fundamental question is which mechanisms are involved in connecting nutrient levels, the cell cycle and chromatin regulation. In this issue, Zhang et al. reveal a signalling cascade whereby nutrient-sensing mTORC1 activates the cell-cycle regulator CDK2, thus leading to nuclear translocation of the metabolic enzyme triosephosphate isomerase 1 (TPI1). In the nucleus, TPI1 alters the levels of acetate and global histone acetylation through the metabolite dihydroxyacetone phosphate.