Proteasome failure promotes positioning of lysosomes around the aggresome via local block of microtubule-dependent transport.

ABSTRACT: Ubiquitinated proteins aggregate upon proteasome failure, and the aggregates are transported to the aggresome. In aggresomes, protein aggregates are actively degraded by the autophagy-lysosome pathway, but why targeting the aggresome promotes degradation of aggregated species is currently unknown. Here we report that the important factor in this process is clustering of lysosomes around the aggresome via a novel mechanism. Proteasome inhibition causes formation of a zone around the centrosome where microtubular transport of lysosomes is suppressed, resulting in their entrapment and accumulation. Microtubule-dependent transport of other organelles, including autophagosomes, mitochondria, and endosomes, is also blocked in this entrapment zone (E-zone), while movement of organelles at the cel

SUBMITTER: Zaarur N 

PROVIDER: S-EPMC3993571 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature