p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death

Geir Bjørkøy; Trond Lamark; Andreas Brech; Heidi Outzen; Maria Perander; Aud Øvervatn; Harald Stenmark; Terje Johansen

doi:10.1083/jcb.200507002

journal article Nov 14, 2005

p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death

Geir Bjørkøy Trond Lamark

Andreas Brech

Heidi Outzen Maria Perander Aud Øvervatn Harald Stenmark

Terje Johansen

The Journal of cell biology Vol. 171 No. 4 pp. 603-614 · Rockefeller University Press

View at Publisher Save 10.1083/jcb.200507002

Abstract

Autophagic degradation of ubiquitinated protein aggregates is important for cell survival, but it is not known how the autophagic machinery recognizes such aggregates. In this study, we report that polymerization of the polyubiquitin-binding protein p62/SQSTM1 yields protein bodies that either reside free in the cytosol and nucleus or occur within autophagosomes and lysosomal structures. Inhibition of autophagy led to an increase in the size and number of p62 bodies and p62 protein levels. The autophagic marker light chain 3 (LC3) colocalized with p62 bodies and coimmunoprecipitated with p62, suggesting that these two proteins participate in the same complexes. The depletion of p62 inhibited recruitment of LC3 to autophagosomes under starvation conditions. Strikingly, p62 and LC3 formed a shell surrounding aggregates of mutant huntingtin. Reduction of p62 protein levels or interference with p62 function significantly increased cell death that was induced by the expression of mutant huntingtin. We suggest that p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to the autophagy machinery.

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Details

Published: Nov 14, 2005
Vol/Issue: 171(4)
Pages: 603-614

Authors

G

Geir Bjørkøy