Lysosomes: a central hub orchestrating metabolic plasticity, signal integration, and proteostasis in adult stem cell quiescence

Abstract The quiescent state of adult stem cells is fundamental to their protection against exogenous damage, the maintenance of stem cell pool stability, and the preservation of long-term regenerative potential in tissues. Elucidating the underlying regulatory mechanisms is of profound significance for stem cell biology and the development of therapeutic interventions for related diseases. Over the past decades, our understanding of the lysosome has evolved from viewing it solely as a degradative compartment to recognizing it as a dynamic regulatory hub for the regulation of stem cell quiescence. This review synthesizes recent research progress on the multidimensional roles of lysosomes in governing the quiescent state of adult stem cells through three core mechanisms: metabolic regulation, signal integration, and the maintenance of proteostasis. We systematically delineate the relevant molecular pathways, key regulatory factors, and their physiological and pathological implications in maintaining tissue homeostasis. This article aims to provide novel perspectives for a deeper understanding of stem cell biology and the formulation of clinical strategies for associated disorders.