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KMID : 0624620210540060305
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BMB Reports
2021 Volume.54 No. 6 p.305 ~ p.310
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Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells
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Park Seul-Ki
Kim Ki-Dae
Haam Kee-Ok
Ban Hyun-Seung
Kim Jung-Ae
Park Byoung-Chul
Park Sung-Goo
Kim Sun-Hong
Kim Jeong-Hoon
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Abstract
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Cereblon (CRBN) is a multi-functional protein that acts as a substrate 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.
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KEYWORD
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Calcium overload, Cell death, CRBN, Mitochondrial dysfunction, ROS
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