Secretory autophagy mediates lysosomal and autophagic degradation for α-synuclein proteostasis.

ABSTRACT: Autophagy has two distinct pathways, degradation and secretion. Autophagic degradation plays a pivotal role in proteostasis. However, the role of autophagic secretion in proteostasis maintenance is not fully understood. Here, we investigate how the blockade of autophagic secretion impairs proteostasis in SH-SY5Y cells. siRNA-mediated knockdown (KD) of a modulator for autophagosome formation, ATG5, BECN1, or FIP200 inhibited autophagic flux and secretion, causing accumulation of Triton X-100-insoluble α-synuclein (α-syn), which is an aggregate-prone protein responsible for neuronal loss in Parkinson's disease. The blockade of autophagic secretion by KD of t-SNARE SNAP23 or STX4 increased autophagic flux for p62 degradation, but these KDs induced enlargement and membrane damage of lysosomes

SUBMITTER: Sawai T 

PROVIDER: S-EPMC12362094 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature