Autophagy-lysosome crosstalk in cellular homeostasis: Mechanisms and implications

Autophagy and lysosomal degradation represent two interconnected quality control systems essential for maintaining cellular homeostasis. This review examines the intricate molecular crosstalk between autophagy and lysosomes, highlighting their coordinated regulation in cellular metabolism, organelle turnover, and stress responses. Autophagy delivers cytoplasmic cargo to lysosomes for degradation, while lysosomes provide the degradative capacity and regulatory signals that modulate autophagy. Recent discoveries have revealed that this bidirectional communication involves multiple regulatory nodes, including transcription factors, nutrient sensors, and membrane contact sites. Disruption of autophagy-lysosome crosstalk contributes to aging, neurodegeneration, metabolic disorders, and cancer. Understanding these mechanisms offers therapeutic opportunities for diseases characterized by impaired cellular homeostasis. This review synthesizes current knowledge on the molecular mechanisms governing autophagy-lysosome interactions and their physiological significance in health and disease.