Autophagy-lysosome pathway (ALP) (ALP)

The autophagy-lysosome pathway (ALP) is a fundamental cellular degradation system responsible for the breakdown and recycling of cytoplasmic components, including damaged organelles and misfolded protein aggregates (PMID: 25855424). This pathway involves the formation of double-membrane vesicles called autophagosomes that capture cargo and subsequently fuse with lysosomes, where acidic hydrolases facilitate degradation (PMID: 21068320). The ALP is essential for maintaining cellular proteostasis and nutrient balance, particularly under conditions of starvation or stress. Dysregulation of this system is implicated in a wide range of diseases, including neurodegenerative disorders like Parkinson's and Alzheimer's, where impaired clearance leads to toxic protein accumulation, and lysosomal storage disorders (PMID: 24560518). In cancer, the pathway exhibits a complex role, potentially suppressing tumor initiation while promoting the survival of established cancer cells under metabolic stress. Therapeutic interventions targeting the ALP include mTOR inhibitors to stimulate autophagy, lysosomotropic agents like hydroxychloroquine to inhibit lysosomal function in tumors, and enzyme replacement therapies for genetic deficiencies (PMID: 28273103).

Other names

Lysosomal compartmentAutophagy pathwayMacroautophagy-lysosome systemLysosomal-autophagy axisLysosomal system

Modulation of the autophagy-lysosome pathway involves several mechanisms: mTOR inhibition to induce autophagy, lysosomal acidification inhibition to block degradation, enzyme replacement therapy to restore deficient lysosomal hydrolases, and pharmacological chaperones to stabilize misfolded enzymes.