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.
Skip Nav Destination
Article navigation
21 November 2005
Article|
November 14 2005
p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
In Special Collection:
JCB65: Autophagy
Geir Bjørkøy,
Geir Bjørkøy
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Search for other works by this author on:
Trond Lamark,
Trond Lamark
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Search for other works by this author on:
Andreas Brech,
Andreas Brech
2Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Search for other works by this author on:
Heidi Outzen,
Heidi Outzen
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Search for other works by this author on:
Maria Perander,
Maria Perander
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Search for other works by this author on:
Aud Øvervatn,
Aud Øvervatn
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Search for other works by this author on:
Harald Stenmark,
Harald Stenmark
2Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Search for other works by this author on:
Terje Johansen
Terje Johansen
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Search for other works by this author on:
Geir Bjørkøy
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Trond Lamark
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Andreas Brech
2Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Heidi Outzen
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Maria Perander
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Aud Øvervatn
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Harald Stenmark
2Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Terje Johansen
1Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
Correspondence to Terje Johansen: [email protected]
Abbreviations used in this paper: EEA1, early endosome antigen 1; LC3, light chain 3; PB1, Phox and Bem1p; siRNA, small interfering RNA; UBA; ubiquitin associated.
Received:
July 01 2005
Accepted:
October 12 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 171 (4): 603–614.
Article history
Received:
July 01 2005
Accepted:
October 12 2005
Citation
Geir Bjørkøy, Trond Lamark, Andreas Brech, Heidi Outzen, Maria Perander, Aud Øvervatn, Harald Stenmark, Terje Johansen; p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death . J Cell Biol 21 November 2005; 171 (4): 603–614. doi: https://doi.org/10.1083/jcb.200507002
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement
Advertisement