CLUH interactome reveals an association to SPAG5 and a proximity to the translation of mitochondrial protein

Hemono, Mickale; Haller, Alexandre; Chicher, Johana; Duchêne, Anne‐Marie; Ngondo, Richard Patryk

doi:10.1101/2021.07.08.451585

Cited by 2 publications

(1 citation statement)

References 53 publications

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“…Drosophila clu, Sod2 and Pink1 mutants have reduced lifespan, although Pink1 mutants live substantially longer than the other two (Duttaroy et al, 2003;Clark et al, 2006;Park et al, 2006;Sen et al, 2013). Clu/Cluh are essential ribonucleoproteins associated with ribosomal proteins that may regulate mRNAs for co-translational import into mitochondria (Sen and Cox 2016;Vardi-Oknin and Arava 2019;Hemono et al, 2022). Clu forms large, dynamic cytoplasmic particles that are sensitive to stress (Cox and Spradling 2009;Sheard et al, 2020;Sheard and Cox 2021).…”

Section: Single Gene Mutations That Affect Mitochondrial Function Dif...mentioning

confidence: 99%

Loss of Drosophila Clueless differentially affects the mitochondrial proteome compared to loss of Sod2 and Pink1

Sen

Cox²

2022

Front. Physiol.

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Mitochondria contain their own DNA, mitochondrial DNA, which encodes thirteen proteins. However, mitochondria require thousands of proteins encoded in the nucleus to carry out their many functions. Identifying the definitive mitochondrial proteome has been challenging as methods isolating mitochondrial proteins differ and different tissues and organisms may have specialized proteomes. Mitochondrial diseases arising from single gene mutations in nucleus encoded genes could affect the mitochondrial proteome, but deciphering which effects are due to loss of specific pathways or to accumulated general mitochondrial damage is difficult. To identify specific versus general effects, we have taken advantage of mutations in three Drosophila genes, clueless, Sod2, and Pink1, which are required for mitochondrial function through different pathways. We measured changes in each mutant’s mitochondrial proteome using quantitative tandem mass tag mass spectrometry. Our analysis identified protein classes that are unique to each mutant and those shared between them, suggesting that some changes in the mitochondrial proteome are due to general mitochondrial damage whereas others are gene specific. For example, clueless mutants had the greatest number of less and more abundant mitochondrial proteins whereas loss of all three genes increased stress and metabolism proteins. This study is the first to directly compare in vivo steady state levels of mitochondrial proteins by examining loss of three pathways critical for mitochondrial function. These data could be useful to understand disease etiology, and how mutations in genes critical for mitochondrial function cause specific mitochondrial proteomic changes as opposed to changes due to generalized mitochondrial damage.

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Section: Single Gene Mutations That Affect Mitochondrial Function Dif...mentioning

confidence: 99%

Loss of Drosophila Clueless differentially affects the mitochondrial proteome compared to loss of Sod2 and Pink1

Sen

Cox²

2022

Front. Physiol.

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The interactome of CLUH reveals its association to SPAG5 and its co-translational proximity to mitochondrial proteins

et al. 2022

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Background Mitochondria require thousands of proteins to fulfill their essential function in energy production and other fundamental biological processes. These proteins are mostly encoded by the nuclear genome, translated in the cytoplasm before being imported into the organelle. RNA binding proteins (RBPs) are central players in the regulation of this process by affecting mRNA translation, stability, or localization. CLUH is an RBP recognizing specifically mRNAs coding for mitochondrial proteins, but its precise molecular function and interacting partners remain undiscovered in mammals. Results Here we reveal for the first time CLUH interactome in mammalian cells. Using both co-IP and BioID proximity-labeling approaches, we identify novel molecular partners interacting stably or transiently with CLUH in HCT116 cells and mouse embryonic stem cells. We reveal stable RNA-independent interactions of CLUH with itself and with SPAG5 in cytosolic granular structures. More importantly, we uncover an unexpected proximity of CLUH to mitochondrial proteins and their cognate mRNAs in the cytosol. We show that this interaction occurs during the process of active translation and is dependent on CLUH TPR domain. Conclusions Overall, through the analysis of CLUH interactome, our study sheds a new light on CLUH molecular function by revealing new partners and by highlighting its link to the translation and subcellular localization of some mRNAs coding for mitochondrial proteins.

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CLUH interactome reveals an association to SPAG5 and a proximity to the translation of mitochondrial protein

Cited by 2 publications

References 53 publications

Loss of Drosophila Clueless differentially affects the mitochondrial proteome compared to loss of Sod2 and Pink1

Loss of Drosophila Clueless differentially affects the mitochondrial proteome compared to loss of Sod2 and Pink1

The interactome of CLUH reveals its association to SPAG5 and its co-translational proximity to mitochondrial proteins

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