Rossetti 2021 Sci Adv

From Bioblast
Publications in the MiPMap
Rossetti G, Ermer JA, Stentenbach M, Siira SJ, Richman TR, Milenkovic D, Perks KL, Hughes LA, Jamieson E, Xiafukaiti G, Ward NC, Takahashi S, Gray N, Viola HM, Hool LC, Rackham O, Filipovska A (2021) A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance. Sci Adv 7:eabi7514.

Β» PMID: 34559558 Open Access

Rossetti Giulia, Ermer Judith A, Stentenbach Maike, Siira Stefan J, Richman Tara R, Milenkovic Dusanka, Perks Kara L, Hughes Laetitia A, Jamieson Emma, Xiafukaiti Gulibaikelamu, Ward Natalie C, Takahashi Satoru, Gray Nicola, Viola Helena M, Hool Livia C, Rackham Oliver, Filipovska Aleksandra (2021) Sci Adv

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 Ξ² 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.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: DE Cologne Larsson NG, AU Perth Filipovska A

Labels: MiParea: Respiration, nDNA;cell genetics 

Organism: Mouse  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, ROX  HRR: Oxygraph-2k 


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