Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Yang, H; Ni, HM; Guo, F; Ding, Y; Shi, YH; Lahiri, P; Fröhlich, LF; Rülicke, T; Smole, C; Schmidt, VC; Zatloukal, K; Cui, Y; Komatsu, M; Fan, J; Ding, WX.
Sequestosome 1/p62 Protein Is Associated with Autophagic Removal of Excess Hepatic Endoplasmic Reticulum in Mice.
J Biol Chem. 2016; 291(36):18663-18674
Doi: 10.1074/jbc.M116.739821
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- Co-Autor*innen der Med Uni Graz
- Fröhlich Leopold F.
- Lahiri Pooja
- Smole Claudia
- Zatloukal Kurt
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- Abstract:
- Xenobiotics exposure increases endoplasmic reticulum (ER) proliferation and cytochrome P-450 (CYP) induction to sustain metabolic requirements. Whether autophagy is essential for the removal of excess ER and CYP and whether an autophagy receptor is involved in this process in mammals remains elusive. In this study, we show that autophagy is induced in mouse livers after withdrawal of the hepatic mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP). Although isolated autophagosomes, autolysosomes, and lysosomes from mouse livers after withdrawal of TCPOBOP contained ER proteins, those in control mouse livers did not. Liver-specific Atg5 knockout mice had higher basal hepatic ER content that was further increased and sustained after withdrawal of TCPOBOP compared with wild-type mice. In addition to regulating ER degradation, our results also suggest that autophagy plays a role in regulating the homeostasis of hepatic CYP because blocking autophagy led to increased CYP2B10 accumulation either at the basal level or following TCPOBOP withdrawal. Furthermore, we found that the autophagy receptor protein sequestosome 1 (SQSTM1)/p62 is associated with the ER. After withdrawal of TCPOBOP, p62 knockout mice had increased ER content in the liver compared with wild-type mice. These results suggest that p62 may act as an autophagy receptor for the autophagic removal of excess ER in the mouse liver. Taken together, our results indicate that autophagy is important for the removal of excess ER and hepatic CYP enzymes in mouse livers, a process associated with the autophagy receptor protein p62. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
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- Autophagy-Related Protein 5 - genetics
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- Pyridines - pharmacology
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