Nutrientsensing

Nutrient sensing refers to the set of cellular and molecular mechanisms by which organisms detect the availability of nutrients such as glucose, amino acids, fatty acids, and vitamins, and translate this information into metabolic and physiological responses. These pathways allow cells to adapt their growth, energy production, and biosynthetic activities to fluctuating environmental conditions.

In eukaryotes, the mechanistic target of rapamycin (mTOR) complex is a central hub that integrates signals from amino acids, growth factors, oxygen, and energy status. Activation of mTORC1 promotes protein synthesis, lipid biosynthesis, and inhibition of autophagy when nutrients are abundant, while its inhibition during scarcity reduces anabolic processes. The AMP‑activated protein kinase (AMPK) senses cellular energy levels through the AMP/ATP ratio; high AMP triggers AMPK activation, leading to increased catabolism, glucose uptake, and mitochondrial biogenesis, and suppressing mTOR signaling.

Amino‑acid–specific sensing involves the GCN2 kinase, which detects uncharged transfer RNAs that accumulate during amino‑acid deprivation. GCN2 phosphorylates eIF2α, attenuating global translation and inducing stress‑responsive genes. Fatty‑acid detection utilizes the peroxisome proliferator‑activated receptors (PPARs) and the liver X receptor (LXR), which bind lipid ligands and regulate genes involved in lipid metabolism and storage.

In prokaryotes, nutrient sensing is mediated by two‑component systems and transcriptional regulators such as the catabolite repression protein CRP, which modulates gene expression in response to glucose levels. These mechanisms coordinate metabolic flux, cell division, and developmental pathways across species.

Dysregulation of nutrient‑sensing pathways is linked to metabolic disorders, cancer, neurodegeneration, and aging. Pharmacological modulation of mTOR, AMPK, or GCN2 is under investigation for therapeutic interventions aimed at restoring metabolic balance and extending health span.