Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells

Cereblon (CRBN) is a multi-functional protein that acts as a sub-strate receptor of the E3 ligase complex and a molecular chaperone. While CRBN is proposed to function in mitochondria, its specific roles are yet to be established. Here, we showed that knockdown of CRBN triggers oxidative stress and...

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Bibliographic Details
Published in:BMB reports 2021-06, Vol.54 (6), p.305-310
Main Authors: Park, Seulki, Kim, Kidae, Haam, Keeok, Ban, Hyun Seung, Kim, Jung-Ae, Park, Byoung Chul, Park, Sung Goo, Kim, Sunhong, Kim, Jeong-Hoon
Format: Article
Language:English
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Summary:Cereblon (CRBN) is a multi-functional protein that acts as a sub-strate receptor of the E3 ligase complex and a molecular chaperone. While CRBN is proposed to function in mitochondria, its specific roles are yet to be established. Here, we showed that knockdown of CRBN triggers oxidative stress and calcium overload in mitochondria, leading to disruption of mitochondrial membrane potential. Notably, long-term CRBN depletion using PROteolysis TArgeting Chimera (PROTAC) induced irreversible mitochondrial dysfunction, resulting in cell death. Our collective findings indicate that CRBN is required for mitochondrial homeostasis in cells.
ISSN:1976-6696
1976-670X
DOI:10.5483/BMBRep.2021.54.6.218