Mitochondrial cereblon functions as a Lon-type protease

Lon protease plays a major role in the protein quality control system in mammalian cell mitochondria. It is present in the mitochondrial matrix and degrades oxidized and misfolded proteins, thereby protecting the cell from various extracellular stresses, including oxidative stress. The intellectual...

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Bibliographic Details
Published in:Scientific reports 2016-07, Vol.6 (1), p.29986-29986, Article 29986
Main Authors: Kataoka, Kosuke, Nakamura, China, Asahi, Toru, Sawamura, Naoya
Format: Article
Language:English
Subjects:
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Cell Death
Cell Line
Humanities and Social Sciences
Humans
Membrane Potential, Mitochondrial
Mitochondria - metabolism
multidisciplinary
Oxidative Stress
Peptide Hydrolases - metabolism
Protease La - metabolism
Protein Sorting Signals
Science
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Summary:Lon protease plays a major role in the protein quality control system in mammalian cell mitochondria. It is present in the mitochondrial matrix and degrades oxidized and misfolded proteins, thereby protecting the cell from various extracellular stresses, including oxidative stress. The intellectual disability-associated and thalidomide-binding protein cereblon (CRBN) contains a large, highly conserved Lon domain. However, whether CRBN has Lon protease-like function remains unknown. Here, we determined if CRBN has a protective function against oxidative stress, similar to Lon protease. We report that CRBN partially distributes in mitochondria, suggesting it has a mitochondrial function. To specify the mitochondrial role of CRBN, we mitochondrially expressed CRBN in human neuroblastoma SH-SY5Y cells. The resulting stable SH-SY5Y cell line showed no apparent effect on the mitochondrial functions of fusion, fission and membrane potential. However, mitochondrially expressed CRBN exhibited protease activity and was induced by oxidative stress. In addition, stably expressed cells exhibited suppressed neuronal cell death induced by hydrogen peroxide. These results suggest that CRBN functions specifically as a Lon-type protease in mitochondria.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep29986