Mitochondrial cereblon functions as a Lon-type protease

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number29986
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016 Jul 15

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Protease La
Mitochondria
Oxidative Stress
Mitochondrial Dynamics
Thalidomide
Neuroblastoma
Intellectual Disability
Quality Control
Membrane Potentials
Hydrogen Peroxide
Carrier Proteins
Proteins
Peptide Hydrolases
Cell Death
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Mitochondrial cereblon functions as a Lon-type protease. / Kataoka, Kosuke; Nakamura, China; Asahi, Toru; Sawamura, Naoya.

In: Scientific Reports, Vol. 6, 29986, 15.07.2016.

Research output: Contribution to journalArticle

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