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 PMID:39786340  

Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function.

Agustian Surya | Blythe Marie Bolton | Reed Rothe | Raquel Mejia-Trujillo | Amanda Leonita | Qiuxia Zhao | Alia Arya | Yue Liu | Rekha Rangan | Yasash Gorusu | Pamela Nguyen | Can Cenik | Elif Sarinay Cenik
The Journal of cell biology | 2025

The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells. Significant mitochondrial morphological differences, upregulation of glutathione transferases, and SKN-1-dependent oxidative stress resistance were observed across mutants. Loss of a Datasingle rps-10 copy reduced mitochondrial activity, energy levels, and oxygen consumption, mirrored by similar reductions in mitochondrial activity and energy levels in lymphoblast cells with 50% lower RPS10 transcripts. Both systems exhibited altered translation efficiency (TE) of mitochondrial electron transport chain components, suggesting a conserved mechanism to adjust mitochondrial protein synthesis under ribosomal stress. Finally, mitochondrial membrane and cytosolic RPs showed significant RNA and TE covariation in lymphoblastoid cells, highlighting the interplay between protein synthesis machinery and mitochondrial energy production.

Pubmed ID: 39786340

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: Welch Foundation,
    Id: F-2133-20230405
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM138340
  • Agency: ODCDC CDC HHS, United States
    Id: P40 OD010440
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM150667
  • Agency: NIGMS NIH HHS, United States
    Id: R35GM138340

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R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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edgeR (tool)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

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Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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N2 (organism)

RRID:WB-STRAIN:WBStrain00000001

Caenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.

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University of Texas at Austin Biological Mass Spectrometry Proteomics Core Facility (service resource)

RRID:SCR_021728

Proteomics and Metabolomics services and collaborative efforts are provided at Biological Mass Spectrometry Facility. We use high resolution Orbitrap mass spectrometers with UPLC at high flow for metabolomics and nanoUPLC for proteomics work. We have Bruker Autoflex for self service MALDI. Our proteomics services are protein ID, quantitation, and modification analysis, with fractionation for deeper coverage and de novo sequencing of mAbs available. We collaborate for customized projects. We have untargeted metabolomics for quantitative or qualitative analysis of extracted metabolites using C18 column.

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