[The role of autophagy in quality control inside neural cells].
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 quality control, particularly in quiescent cells such as neurons. 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. Neural cell-specific Atg5-deficient mice, Atg5(flox/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 generation of aggregates and inclusions. This study emphasizes that basal autophagy is important even in individuals who do not express neurodegenerative disease-associated mutant proteins. Further, the primary targets of autophagy are diffused cytosolic proteins, not protein aggregates themselves. These data suggest that basal autophagy has a critical role in intracellular protein quality control under normal conditions, which is independent of the role of induced autophagy as an adaptation to starvation.
Mizushima
Noboru
N
Department of Physiology and Cell Biology, Tokyo Medical and Dental University.
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*