RRC ID 47266
著者 Kataoka K, Nakamura C, Asahi T, Sawamura N.
タイトル Mitochondrial cereblon functions as a Lon-type protease.
ジャーナル Sci Rep
Abstract 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.
巻・号 6
ページ 29986
公開日 2016-7-15
DOI 10.1038/srep29986
PII srep29986
PMID 27417535
PMC PMC4945938
MeSH Adaptor Proteins, Signal Transducing Cell Death Cell Line Humans Membrane Potential, Mitochondrial Mitochondria / metabolism* Oxidative Stress Peptide Hydrolases / metabolism* Protease La / metabolism* Protein Sorting Signals Ubiquitin-Protein Ligases
IF 3.998
引用数 9
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
遺伝子材料 Genome Network Project Human cDNA IRAL038I16 (HGY095408).