| First Author | Rossetti G | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 39 | Pages | eabi7514 |
| PubMed ID | 34559558 | Mgi Jnum | J:313718 |
| Mgi Id | MGI:6788003 | Doi | 10.1126/sciadv.abi7514 |
| Citation | Rossetti G, et al. (2021) A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance. Sci Adv 7(39):eabi7514 |
| abstractText | 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. |
