Article ; Online: The E3 ubiquitin ligase FBXL6 controls the quality of newly synthesized mitochondrial ribosomal proteins.
2023 Volume 42, Issue 6, Page(s) 112579
Abstract: In mammals, about 99% of mitochondrial proteins are synthesized in the cytosol as precursors that are subsequently imported into the organelle. The mitochondrial health and functions rely on an accurate quality control of these imported proteins. Here, ... ...
| Abstract | In mammals, about 99% of mitochondrial proteins are synthesized in the cytosol as precursors that are subsequently imported into the organelle. The mitochondrial health and functions rely on an accurate quality control of these imported proteins. Here, we show that the E3 ubiquitin ligase F box/leucine-rich-repeat protein 6 (FBXL6) regulates the quality of cytosolically translated mitochondrial proteins. Indeed, we found that FBXL6 substrates are newly synthesized mitochondrial ribosomal proteins. This E3 binds to chaperones involved in the folding and trafficking of newly synthesized peptide and to ribosomal-associated quality control proteins. Deletion of these interacting partners is sufficient to hamper interactions between FBXL6 and its substrate. Furthermore, we show that cells lacking FBXL6 fail to degrade specifically mistranslated mitochondrial ribosomal proteins. Finally, showing the role of FBXL6-dependent mechanism, FBXL6-knockout (KO) cells display mitochondrial ribosomal protein aggregations, altered mitochondrial metabolism, and inhibited cell cycle in oxidative conditions. |
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| MeSH term(s) | Mammals/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Protein Domains ; Ribosomal Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Humans |
| Chemical Substances | Mitochondrial Proteins ; Ribosomal Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; FBXL6 protein, human |
| Language | English |
| Publishing date | 2023-06-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2649101-1 |
| ISSN | 2211-1247 ; 2211-1247 |
| ISSN (online) | 2211-1247 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2023.112579 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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