Intracellular quality control by autophagy: How does autophagy prevent neurodegeneration?

Noboru Mizushima*, Taichi Hara

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)


Autophagy is an intracellular bulk degradation process, through which a portion of cytoplasm is delivered to lysosomes to be degraded. In many organisms, the primary role of autophagy is adaptation to starvation. However, we have found that autophagy is also important for intracellular protein quality control. Atg5-/- mice die shortly after birth due, at least in part, to nutrient deficiency. These mice also exhibit an intracellular accumulation of protein aggregates in neurons and hepatocytes. We now report the generation of neural cell-specific Atg5-deficient mice. Atg5flox/flox;Nestin-Cre mice show progressive deficits in motor function and degeneration of some neural cells. In autophagy-deficient cells, diffuse accumulation of abnormal proteins occurs, followed by the generation of aggregates and inclusions. This study emphasizes the point that basal autophagy is important even in individuals who do not express neurodegenerative disease-associated mutant proteins. Furthermore, the primary targets of autophagy are diffuse cytosolic proteins, not protein aggregates themselves.

Original languageEnglish
Pages (from-to)302-304
Number of pages3
Issue number4
Publication statusPublished - 2006
Externally publishedYes


  • Aggregate
  • Atg5
  • Inclusion body
  • Neurodegeneration
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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