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Hum Mol Genet. 2008 Aug 15;17(16):2570-82. doi: 10.1093/hmg/ddn157. Epub 2008 May 23.

Autophagy-mediated clearance of aggresomes is not a universal phenomenon.

Author information

1
Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore.

Abstract

Aggresomes are juxtanuclear inclusion bodies that have been proposed to act as staging grounds for the disposal of protein aggregates via the autophagic route. To examine whether the composition of an aggresome influences its clearance by autophagy, we ectopically expressed a variety of aggregation-prone proteins in cultured cells to generate aggresomes that differ in their protein content. We found that whereas aggresomes generated in cells expressing mutant huntingtin or mutant tau, or co-expressing synphilin-1 and alpha-synuclein, are amenable to clearance by autophagy, those produced in AIMP2 (p38)- or mutant desmin-expressing cells are apparently resistant to autophagic clearance. Notably, AIMP2 (p38)- and desmin-positive inclusions fail to recruit key components of the autophagic/lysosomal system. However, by altering the composition of inclusions, 'autophagy-resistant' aggresomes could be rendered 'autophagy-susceptible'. Taken together, our results demonstrate that not all aggresomes are efficiently primed for autophagic clearance and highlight a certain degree of selectivity for the supposedly non-discriminative pathway.

PMID:
18502787
PMCID:
PMC2722889
DOI:
10.1093/hmg/ddn157
[Indexed for MEDLINE]
Free PMC Article

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