Autophagy-lysosome system (ALS) (ALS)

The autophagy-lysosome system (ALS) is a fundamental intracellular degradation pathway responsible for the clearance and recycling of long-lived proteins, damaged organelles, and misfolded protein aggregates (Mizushima & Komatsu, 2011). This system operates through the formation of double-membrane autophagosomes that sequester cytoplasmic components and subsequently fuse with lysosomes, where acidic hydrolases break down the cargo into basic nutrients (Klionsky et al., 2021). The ALS is essential for maintaining cellular proteostasis and metabolic balance, particularly during periods of nutrient deprivation or oxidative stress. Dysregulation of the ALS is implicated in a wide range of human diseases, including neurodegenerative disorders like Alzheimer's and Parkinson's, where impaired clearance leads to toxic protein accumulation (Nixon, 2013). In oncology, the system plays a dual role, acting as a tumor suppressor during early tumorigenesis but facilitating the survival of established cancer cells under hypoxic or nutrient-poor conditions (Amaravadi et al., 2019). Therapeutic strategies targeting the ALS include the use of mTOR inhibitors to stimulate autophagy and lysosomotropic agents like hydroxychloroquine to inhibit degradative flux, making it a versatile but complex target for drug development.

Other names

Autophagy-lysosomal pathwayALPMacroautophagy-lysosome pathwayLysosomal degradation system

Inhibition of mTORC1 to stimulate autophagosome formation; inhibition of lysosomal acidification to prevent cargo degradation; activation of TFEB to increase lysosomal biogenesis and autophagy gene expression.