TOR signalling articles from across Nature Portfolio

Unmet expectations, a previously uncharacterized fly protein, is a SAM sensor for the mTORC1 pathway. Tracing the evolution of Unmet reveals that the pathway uses the GATOR2 complex to capture and repurpose ancestral enzymes as nutrient sensors.

The liver is segregated into spatially organized areas that serve distinct functions, though how these zones are patterned remains unclear. Here they show that mTORC1 controls spatial segregation of liver metabolic functions via modulation of Wnt signaling, and find that impaired zonation is also observed in pigs given total parenteral nutrition.

The different compartments of the mammary stem cell hierarchy develop into distinct breast cancer subtypes as a result of specific genetic lesions. A recent study identifies aberrant ERBB3^low luminal progenitors with altered proteostasis and translation as the cell of origin of BRCA2-mutant breast cancer.

Okreglak et al. explore the molecular mechanisms that link organellar pH dynamics with the cell cycle, and find that vacuolar pH oscillates during cell cycle phases to ensure an adequate supply of amino acids during cell division. This study offers metabolic insight into the fundamental mechanisms that couple amino acid availability to the cell cycle through pH fluctuations.

Cells use various metabolic pathways to synthesize the building blocks for growth and proliferation. To ensure balanced growth, these biosynthetic processes must be tightly coordinated. We describe a molecular machinery that senses the cellular capacity to make lipids to regulate other biosynthetic processes — such as protein synthesis — accordingly.

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.