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Lecture "Regulation of the mitochondrial functions by the Ubiquitin protéasome system: molecular bases and physiopathological relevance"

Most mitochondrial proteins are synthesized in the cytosol and imported into mitochondria. Recently, we have pointed out the role of the ubiquitin-proteasome system in the regulation of mitochondrial metabolism [1]. Here, we have identified a family of E3s that participate to the control quality of newly synthesized mitochondrial proteins in mammalian cells. We have found that specific deletion of these E3s induced altered mitochondrial metabolism, inhibited cell cycle progression in oxidative condition, and induce aggregation of mitochondrial proteins.  Interestingly, these enzymes can be located to various compartment including the nucleus, the cytosol and the mitochondria but they share common interacting proteins including various chaperones and ribosome-associated quality control proteins [2]. Using pulsed Silac approaches we showed that they interact preferentially with neosynthesized proteins including mitochondrial ribosomal Proteins (MRPs). Combining the localization and their interactome, our results suggest that this family of E3s participates to the quality control mechanisms of neosynthesized mitochondrial proteins in coordination with translation-associated quality control processes.

[1]     J. Lavie et al., “Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism,” Cell Rep., vol. 23, no. 10, pp. 2852–2863, 2018, doi: 10.1016/j.celrep.2018.05.013.

[2]     C. A. P. Joazeiro, “Mechanisms and functions of ribosome-associated protein quality control,” Nat. Rev. Mol. Cell Biol., vol. 20, no. 6, pp. 368–383, 2019, doi: 10.1038/s41580-019-0118-2.


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