Nutrients and Their Role in Autophagy Regulation

Abstract Autophagy is a fundamental catabolic pathway that maintains cellular homeostasis through the degradation and recycling of intracellular components in response to nutrient limitation and metabolic stress. Increasing evidence indicates that autophagy is tightly regulated by cellular metabolism, with nutrients and metabolites acting not only as energy substrates and biosynthetic intermediates, but also as signaling molecules that directly modulate the autophagic machinery. In this review, we discuss how different metabolites regulate autophagy through interconnected nutrient- and energy-sensing pathways. We further examine how these metabolic signals coordinate distinct stages of autophagosome biogenesis and autophagic flux under conditions of nutrient deprivation or energy stress. Collectively, metabolite-autophagy crosstalk emerges as a central mechanism that enables cells to balance metabolic demand with intracellular resource availability, while its dysregulation contributes to metabolic imbalance and age-associated pathology.