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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249880/ https://www.ncbi.nlm.nih.gov/pubmed/33408001 http://dx.doi.org/10.5483/BMBRep.2021.54.6.218 |
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author | Park, Seulki Kim, Kidae Haam, Keeok Ban, Hyun Seung Kim, Jung-Ae Park, Byoung Chul Park, Sung Goo Kim, Sunhong Kim, Jeong-Hoon |
author_facet | Park, Seulki Kim, Kidae Haam, Keeok Ban, Hyun Seung Kim, Jung-Ae Park, Byoung Chul Park, Sung Goo Kim, Sunhong Kim, Jeong-Hoon |
author_sort | Park, Seulki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8249880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-82498802021-07-12 Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells Park, Seulki Kim, Kidae Haam, Keeok Ban, Hyun Seung Kim, Jung-Ae Park, Byoung Chul Park, Sung Goo Kim, Sunhong Kim, Jeong-Hoon BMB Rep Article 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. Korean Society for Biochemistry and Molecular Biology 2021-06-30 2021-06-30 /pmc/articles/PMC8249880/ /pubmed/33408001 http://dx.doi.org/10.5483/BMBRep.2021.54.6.218 Text en Copyright © 2021 by the The Korean Society for Biochemistry and Molecular Biology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Park, Seulki Kim, Kidae Haam, Keeok Ban, Hyun Seung Kim, Jung-Ae Park, Byoung Chul Park, Sung Goo Kim, Sunhong Kim, Jeong-Hoon Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells |
title | Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells |
title_full | Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells |
title_fullStr | Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells |
title_full_unstemmed | Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells |
title_short | Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells |
title_sort | long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249880/ https://www.ncbi.nlm.nih.gov/pubmed/33408001 http://dx.doi.org/10.5483/BMBRep.2021.54.6.218 |
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