MICROAUTOPHAGY OF CYTOSOLIC PROTEINS BY LATE ENDOSOMES

By R. Sahu, Susmita Kaushik, Cristina C. Clement, E. S. Cannizzo, Brian Scharf, A. Follenzi, I. Potolicchio, E. Nieves, A. Cuervo, L. Santambrogio. Developmental Cell, 2011

847 citations recorded by the source corpus.

Summary Autophagy delivers cytosolic components to lysosomes for their degradation. The delivery of autophagic cargo to late endosomes for complete or partial degradation has also been described. In this report, we present evidence that distinct autophagic mechanisms control cytosolic protein delivery to late endosomes and identify a microautophagy-like process that delivers soluble cytosolic proteins to the vesicles of late endosomes/multivesicular bodies (MVB). This microautophagy-like process has selectivity and is distinct from chaperone-mediated autophagy that occurs in lysosomes. Endosomal microautophagy occurs during MVB formation, relying on the ESCRT I and III systems for formation of the vesicles in which the cytosolic cargo is internalized. Protein cargo selection is mediated by the chaperone hsc70 and requires the cationic domain of hsc70 for electrostatic interactions with the endosomal membrane. Therefore, we propose that endosomal microautophagy shares molecular components with both the endocytic and autophagic pathways.

View Paper: https://www.semanticscholar.org/paper/bb2c4618b3e822a50eda4226cf7d938a37e97228

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Citations in the corpus

• Biogenesis and secretion of exosomes. (2014, unknown): “Ceramide was proposed to induce inward curvature of the limiting membrane of MVBs to form ILVs.”
• Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. (2014, background): “For soluble cargoes, ubiquitinated (Buschow et al. 2005) and KFERQ-containing proteins (Sahu et al. 2011) are abundant in exosomes.”
• An Overview of Autophagy: Morphology, Mechanism, and Regulation (2014, background): “A very recent study presented evidence that a microautophagy-like process called endosomal microautophagy transports soluble cytosolic proteins to the vesicles of late endosomal multivesicular bodies (123).”
• Autophagy-Independent Functions of the Autophagy Machinery (2019, background): “In some cases, ATG7 seems to be required for optimal exosome release (potentially linked to its role in ATG3-ATG12 conjugation) (Murrow et al., 2015; Shrivastava et al., 2015), while in other settings, exosome release operates normally in the absence of ATG7 (Guo et al., 2017; Sahu et al., 2011).”
• Microautophagy: lesser-known self-eating (2011, unknown): “Three forms of complexes function in the MVB pathway: ESCRT (endosomal sorting complex required for transport) -I, -II, and -III [68, 69].”