LAVIE, Julie; LALOU, Claude; MAHFOUF, Walid; DUPUY, Jean-William; LACAULE, Aurélie; CYWINSKA, Agata Ars; LACOMBE, Didier; DUCHENE, Anne-Marie; RAYMOND, Anne-Aurélie; REZVANI, Hamid Reza; NGONDO, Richard Patryk; BÉNARD, Giovanni

doi:10.1016/j.celrep.2023.112579

Voir/Ouvrir

MRGM_Cell.Rep_2023_Lavie.pdf (5.700Mo)

Métadonnées

Afficher la notice complète

Licence d’utilisation du document

LAVIE, Julie
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]

LALOU, Claude
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]

MAHFOUF, Walid
BoRdeaux Institute in onCology [Inserm U1312 - BRIC]

Langue

Article de revue

Ce document a été publié dans

Cell Reports. 2023-06-01, vol. 42, n° 6, p. 112579

Résumé en anglais

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.< Réduire

Mots clés en anglais

Mammals

Mitochondria

Mitochondrial Proteins

Protein Domains

Ribosomal Proteins

Ubiquitin-Protein Ligases

Humans