Digest it all: the lysosomal turnover of cytoplasmic aggregates

Mario Mauthe, Harm H Kampinga, Mark S Hipp, Fulvio Reggiori

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8 Citations (Scopus)

Abstract

Aggrephagy describes the selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. In this process, protein aggregates and conglomerates are polyubiquitinated and then sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) are central to aggrephagy and physically bind to both ubiquitin and the autophagy machinery, thus linking the cargo to the forming autophagosomal membrane. Because the accumulation of protein aggregates is associated with cytotoxicity in several diseases, a better molecular understanding of aggrephagy might provide a conceptual framework to develop therapeutic strategies aimed at delaying the onset of these pathologies by preventing the buildup of potentially toxic aggregates. We review recent advances in our knowledge about the mechanism of aggrephagy.

Original languageEnglish
JournalTrends in Biochemical Sciences
Volume48
Issue3
Pages (from-to)216-228
Number of pages13
ISSN0968-0004
DOIs
Publication statusPublished - Mar 2023

Keywords

  • cellular protein quality control
  • chaperone-mediated autophagy
  • macro-autophagy
  • micro-autophagy
  • p62 bodies
  • selective autophagy receptors
  • Protein Aggregates
  • Autophagosomes
  • Sequestosome-1 Protein/metabolism
  • Lysosomes/metabolism
  • Autophagy

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