Nonubiquitous autophagy

Cells use autophagy for bulk degradation, in what is often thought of as a nonspecific process. That perception, however, might not be accurate, according to data from Bjørkøy et al. (page 603). Some autophagy substrates are polyubiquitinated and appear to be targeted for destruction.

Protein aggregates, such as those found in Huntington's disease, contain polyubiquitinated proteins, as well as the polyubiquitin-binding protein p62.

The team found that p62 accumulation into protein aggregates depended on its polyubiquitin binding domain and on a polymerization domain, PB1, which allows large chains of p62 to form. p62 also colocalized with LC3, a protein that binds to the autophagosome membrane. Moreover, inhibition of autophagy blocked p62 degradation.

In cells expressing a mutant huntingtin protein, aggregates containing p62 and LC3 were even more common than in the...