Microautophagy of cytosolic proteins by late endosomes

Dev Cell. 2011 Jan 18;20(1):131-9. doi: 10.1016/j.devcel.2010.12.003.

Abstract

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 (MVBs). 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy*
  • Cytosol / metabolism*
  • DNA-Binding Proteins / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • HSC70 Heat-Shock Proteins / metabolism
  • Lysosomal-Associated Membrane Protein 2 / metabolism
  • Lysosomes / metabolism
  • Lysosomes / ultrastructure
  • Mice
  • Multivesicular Bodies / metabolism
  • Multivesicular Bodies / ultrastructure
  • NIH 3T3 Cells
  • Protein Binding
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • HSC70 Heat-Shock Proteins
  • Lysosomal-Associated Membrane Protein 2
  • Transcription Factors
  • Tsg101 protein