Dataset Information

The E3 ubiquitin ligase FBXL6 controls the quality of newly synthesized mitochondrial ribosomal proteins

ABSTRACT: Most mitochondrial proteins are synthetized in the cytosol and imported into mitochondria. Here, we demonstrate that the E3 ubiquitin ligase F-box/LRR-repeat protein 6 (FBXL6) controls the quality of newly synthesized mitochondrial ribosomal proteins in mammalian cells. We found that cells lacking FBXL6 display altered mitochondrial metabolism, inhibited cell cycle progression, and present mitochondrial ribosomal protein aggregates. We found that FBXL6 interacts with mitochondrial ribosome precursors, various chaperones, and ribosome-associated quality control proteins and unlike the mitochondrial E3 ubiquitin ligase FBXL4, FBXL6 is located in the cytosol. Our findings demonstrate that FBXL6 is recruited to aggregates containing defective mitochondrial ribosomal proteins and chaperones. Deletion of FBXL6 specifically impaired the degradation of these defective proteins. Hence, our results suggest that FBLX6 participates in the quality control mechanisms of neosynthesized mitochondrial ribosomal proteins in coordination with translation-associated quality control processes.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Johana Chicher

LAB HEAD: Patryk Ngondo

PROVIDER: PXD028161 | Pride | 2025-09-17

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	2020_S46_PNgondo_FBLX6-30mn_S19.mgf	Mgf
	2020_S46_PNgondo_FBLX6-30mn_S19.raw	Raw
	2020_S46_PNgondo_FBLX6-30mn_S20.mgf	Mgf
	2020_S46_PNgondo_FBLX6-30mn_S20.raw	Raw
	2020_S46_PNgondo_FBLX6-30mn_S21.mgf	Mgf

Items per page:

1 - 5 of 25

Similar Datasets

Project description:Ischemic stroke induces pathological glycogen deposition in astrocytes, but its role in post-injury neural dysfunction remains undefined. We firstly intend to identify the glycogen granule proteome after ischemic stroke via glycogen pulldown for protein mass spectrometry detection. KEGG pathway analysis of the glycogen granule proteome revealed highly enriched mitochondrial-related functional signals, such as respiratory chain complexes, mitochondrial respirasomes, and mitochondrial membrane protein complexes. GO functional annotation of biological processes revealed enrichment of genes related to mitochondrial electron transport, respiratory chain complexes, and mitochondrial ATP synthesis. To explore detailed mitochondrial biological processes in detail, we summarized mitochondrial function gene sets from the mitoproteome database and intersected them with many glycogen-enriched proteins. The data revealed that glycogen stress granules are related mainly to oxidative phosphorylation subunits, assembly factors and electron carriers; mitochondrial dynamics (such as MFF, DNM1L, and GDAP1), homeostasis, and quality control (such as AFG3L2, CLPB, and ATAD3A). Evidence from our experimental data has shown that ATAD3A oligomerization requires the accumulation of astrocytic glycogen stress granules. Under physiological conditions, ATAD3A does not oligomerize, and mitochondria do not exhibit obvious dysfunction in nonglycogen stress granule-deposited cells. To explore what candidate partners are involved with ATAD3A. The proximity-biotinylating enzyme TurboID was reconstituted with ATAD3A to detect biotinylated proteins adjacent to ATAD3A. We next constructed a stable ATAD3A-TurboID cell line (or primary astrocytes). Pulldown biotinylated proteins were subjected to quantitative high-resolution mass spectrometry. Based on the above mass spectrometry data and a series of experimental results, we found that: glycogen-laden astrocytes in the ischemic penumbra undergo HDAC3-dependent mitochondrial fragmentation via a stress granule-mediated mechanism, exacerbating neuronal injury and hindering functional recovery. Mechanistic studies demonstrate that glycogen aggregates sequester cytoplasmic HDAC3, enabling its translocation to mitochondria. There, HDAC3 deacetylates outer mitochondrial membrane protein ATAD3A, promoting oligomerization-driven mitochondrial fission. Astrocyte-specific ATAD3A ablation prevents stroke-induced synaptic disorganization, neural circuit disruption, and cognitive deficits. Therapeutically, combined administration of cotadutide (a glycogen-depleting GLP-1/GCGR agonist) and HDAC3 inhibitor RGFP966 reverses glycogen accumulation, rescues mitochondrial architecture/function, and restores synaptic plasticity and circuit reorganization, thereby accelerating sensorimotor recovery.

Dataset Information

The E3 ubiquitin ligase FBXL6 controls the quality of newly synthesized mitochondrial ribosomal proteins

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets