In addition to bulk protein degradation, Microautophagy (MI) can also target KFERQ motif protein substrates similar to Chaperone Mediated Autophagy (CMA). However, MI is distinct from CMA in that it occurs during late endosomes/multivesicular bodies formation. Upon binding with Hspa8, substrates are transported from the cytosol to late endosomes. HSPA8 binds with the phospholipids on the late endosomal membrane. Subsequently, the substrate is transported into the lumen via endosomal sorting complexes required for transport (ESCRTI and ESCRTIII systems) (Sahu R et al. 2011). This event is represented as a black box since the precise molecular mechanism of the substrate transport into the endosomal lumen is unclear. Experiments confirming this event were performed in mouse.
Cuervo, AM, Potolicchio, I, Cannizzo, ES, Follenzi, A, Scharf, B, Kaushik, S, Santambrogio, L, Sahu, R, Nieves, E, Clement, CC
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