Microautophagy (MI) is a non-selective autophagic pathway that involves internalisation of cytosolic cargo through invaginations of the lysosomal membrane. MI can be induced by nitrogen starvation and complements other related self-eating processes such as Macroautophagy (MA) and Chaperone Mediated Autophagy (CMA). MI can degrade cell organelles and bulk cytosolic proteins directly via the lysosome and late endosome. MI can also target substrates with KFERQ motifs with the help of HSPA8 (Li W W et al. 2012).
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Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds substrate proteins in the cytosol. HSPA8 recognizes a motif based on the charge of the amino acids (Chiang H et al. 1989, Dice JF et al. 1990). This allows the motif to have multiple sequence possibilities and also create a motif through post-translational modifications such as phosphorylation and acetylation. Once bound with HSPA8, the substrates are targeted to the lysosome or endosome.
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.
Microautophagy (MI) can target KFERQ motif containing protein substrates to endosomal degradation. Upon binding with HSPA8, substrates are transported from the cytosol to late endosomes. Here, HSPA8 binds with the phospholipids on the late endosomal membrane. This interaction facilitates the vesicle-mediated transport of HSPA8:substrate complex into the late endosomes for degradation (Sahu R et al. 2011). Experiments confirming this interaction were performed in mouse cells.
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autophagic
substrateschaperone mediated
autophagyAnnotated Interactions
autophagic
substratesautophagic
substrateschaperone mediated
autophagy