Journal article
A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance
Science Advances, Vol.7(39), Art. eabi7514
2021
Abstract
Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet. The variant did not influence mitochondrial gene expression markedly, but instead, it reduced mitochondrial calcium that lowered insulin release from the pancreatic islet β cells of the Mrpp3 variant mice. Reduced insulin secretion resulted in lower insulin levels that contributed to imbalanced metabolism and liver steatosis in the Mrpp3 variant mice on a high-fat diet. Our findings reveal that the MRPP3 variant may be a predisposing factor to insulin resistance and metabolic disease in the human population.
Details
- Title
- A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance
- Authors/Creators
- G. Rossetti (Author/Creator) - The University of Western AustraliaJ.A. Ermer (Author/Creator) - The University of Western AustraliaM. Stentenbach (Author/Creator) - The University of Western AustraliaS.J. Siira (Author/Creator) - The University of Western AustraliaT.R. Richman (Author/Creator) - The University of Western AustraliaD. Milenkovic (Author/Creator) - Max Planck Institute for Biology of AgeingK.L. Perks (Author/Creator) - The University of Western AustraliaL.A. Hughes (Author/Creator) - The University of Western AustraliaE. Jamieson (Author/Creator) - The University of Western AustraliaG. Xiafukaiti (Author/Creator) - University of TsukubaN.C. Ward (Author/Creator) - The University of Western AustraliaS. Takahashi (Author/Creator) - University of TsukubaN. Gray (Author/Creator) - Murdoch UniversityH.M. Viola (Author/Creator) - The University of Western AustraliaL.C. Hool (Author/Creator) - The University of Western AustraliaO. Rackham (Author/Creator) - Harry Perkins Institute of Medical ResearchA. Filipovska (Author/Creator) - Harry Perkins Institute of Medical Research
- Publication Details
- Science Advances, Vol.7(39), Art. eabi7514
- Publisher
- AAAS
- Identifiers
- 991005540164307891
- Copyright
- © 2021 The Authors.
- Murdoch Affiliation
- Australian National Phenome Centre; Centre for Computational and Systems Medicine; Health Futures Institute
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
149 File views/ downloads
142 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.197 Molecular & Cell Biology - Mitochondria
- 1.197.564 Mitochondrial Function
- Web Of Science research areas
- Biochemistry & Molecular Biology
- ESI research areas
- Molecular Biology & Genetics