Adaptive crosstalk between polyamine metabolism, translation, and autophagy sustains energy homeostasis in mammals during starvation: a scoping review.

Mammalian cells tightly regulate the shift between catabolism and anabolism to maintain energy homeostasis during starvation. Among other adaptations, cells adapt to nutrient restriction by downregulating translation, the most energy consuming cellular process, and inducing autophagy(definition). Polyamines are ubiquitous small polycationic endogenous metabolites indispensable for cellular growth and viability. They regulate both autophagy and translation processes, coordinating an intriguing metabolic hub during cellular adaptation to starvation. Recent studies have highlighted a complex role for polyamines during starvation and a growing body of evidence underscores various nutrients and nutrient-sensing pathways that modulate autophagy through their influence on the mammalian target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) complex 1 (mTORC1) signaling. mTORC1 is a master regulator of cellular anabolism, including translation. Less explored is how these coordinated systems adapt and respond to starvation. This scoping review explores how changes in polyamine metabolism and related molecules orchestrate the adaptive crosstalk between autophagy, mTORC1, and translation to ensure that the mammalian cell conserves energy to maintain essential cellular functions during starvation. Our review highlights that spermidine and one of its major cellular targets, translation initiation factor 5A (eIF5A), facilitate translation of transcription factor EB (TFEB) to induce autophagy during starvation. Starvation suppresses mTORC1 activity, leading to reduced ribosome biogenesis and translation while promoting autophagy to meet cellular energy demands. We discuss the adaptive mechanisms by which reduced levels of acetyl-CoA, amino acids, EP300, glucose, insulin, and S-adenosylmethionine inhibit mTORC1 and simultaneously induce autophagy. Additionally, we describe the adaptive role that glucagon, Sestrin2, and urea play to inhibit mTORC1 and how eIF5A, glucagon, spermidine, and TFEB induce autophagy.