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Mitochondrial - nuclear genetic interaction modulates whole body metabolism, adiposity and gene expression in vivo.

EBioMedicine | 2018

We hypothesized that changes in the mitochondrial DNA (mtDNA) would significantly influence whole body metabolism, adiposity and gene expression in response to diet. Because it is not feasible to directly test these predictions in humans we used Mitochondrial-Nuclear eXchange mice, which have reciprocally exchanged nuclear and mitochondrial genomes between different Mus musculus strains. Results demonstrate that nuclear-mitochondrial genetic background combination significantly alters metabolic efficiency and body composition. Comparative RNA sequencing analysis in adipose tissues also showed a clear influence of the mtDNA on regulating nuclear gene expression on the same nuclear background (up to a 10-fold change in the number of differentially expressed genes), revealing that neither Mendelian nor mitochondrial genetics unilaterally control gene expression. Additional analyses indicate that nuclear-mitochondrial genome combination modulates gene expression in a manner heretofore not described. These findings provide a new framework for understanding complex genetic disease susceptibility.

Pubmed ID: 30232024 RIS Download

Research resources used in this publication

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Associated grants

  • Agency: NIAMS NIH HHS, United States
    Id: T32 AR069516
  • Agency: NHLBI NIH HHS, United States
    Id: R21 HL106199
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK079626
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007918
  • Agency: NIA NIH HHS, United States
    Id: P30 AG050886
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL103859
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL094518

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Entrez Gene (tool)

RRID:SCR_002473

Database for genomes that have been completely sequenced, have active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. Includes nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases. All entries follow NCBI's format for data collections. Content of Entrez Gene represents result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. Content is updated as new information becomes available.

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RRID:SCR_016137

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WebGestalt: WEB-based GEne SeT AnaLysis Toolkit (tool)

RRID:SCR_006786

Web based gene set analysis toolkit designed for functional genomic, proteomic, and large-scale genetic studies from which large number of gene lists (e.g. differentially expressed gene sets, co-expressed gene sets etc) are continuously generated. WebGestalt incorporates information from different public resources and provides a way for biologists to make sense out of gene lists. This version of WebGestalt supports eight organisms, including human, mouse, rat, worm, fly, yeast, dog, and zebrafish.

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RRID:SCR_015687

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