Autophagy–Lysosome Pathway (ALP)

The autophagy–lysosome pathway (ALP) is a fundamental intracellular degradation system responsible for the breakdown and recycling of macromolecules, damaged organelles, protein aggregates, and other cellular debris. This process is essential for maintaining cellular homeostasis, especially under stress conditions or during nutrient deprivation. It involves the formation of autophagosomes, their fusion with lysosomes, and the subsequent degradation of the autophagosomal contents. The pathway encompasses several forms, including macroautophagy, selective autophagy (e.g., mitophagy, aggrephagy), chaperone-mediated autophagy (CMA), and microautophagy. Key molecular players include ATG proteins, LC3/ATG8 family members, SNAREs, and RAB GTPases. The ALP serves several critical functions, including the degradation/recycling of long-lived or misfolded proteins, the removal of damaged organelles, and defense against pathogens. Failure or dysregulation leads to accumulation of toxic materials implicated in neurodegenerative diseases like Parkinson’s disease. Modulating this pathway has emerged as a promising therapeutic strategy in neurodegenerative disorders.

Other names

Autophagy pathwayLysosomal degradation pathwayMacroautophagySelective autophagyMitophagyAggrephagyChaperone-mediated autophagyCMAMicroautophagyPexophagyLipophagyXenophagy

Modulation of autophagy flux (e.g., induction or inhibition of autophagy)