| First Author | De Gaetano A | Year | 2020 |
| Journal | J Clin Med | Volume | 9 |
| Issue | 6 | PubMed ID | 32521756 |
| Mgi Jnum | J:321165 | Mgi Id | MGI:6884624 |
| Doi | 10.3390/jcm9061783 | Citation | De Gaetano A, et al. (2020) Impaired Mitochondrial Morphology and Functionality in Lonp1(wt/-) Mice. J Clin Med 9(6):1783 |
| abstractText | LONP1 is a nuclear-encoded mitochondrial protease crucial for organelle homeostasis; mutations of LONP1 have been associated with Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies (CODAS) syndrome. To clarify the role of LONP1 in vivo, we generated a mouse model in which Lonp1 was ablated. The homozygous Lonp(-/-) mouse was not vital, while the heterozygous Lonp1(wt/-) showed similar growth rate, weight, length, life-span and histologic features as wild type. Conversely, ultrastructural analysis of heterozygous enterocytes evidenced profound morphological alterations of mitochondria, which appeared increased in number, swollen and larger, with a lower complexity. Embryonic fibroblasts (MEFs) from Lonp1(wt/-) mice showed a reduced expression of Lonp1 and Tfam, whose expression is regulated by LONP1. Mitochondrial DNA was also reduced, and mitochondria were swollen and larger, albeit at a lesser extent than enterocytes, with a perinuclear distribution. From the functional point of view, mitochondria from heterozygous MEF showed a lower oxygen consumption rate in basal conditions, either in the presence of glucose or galactose, and a reduced expression of mitochondrial complexes than wild type. In conclusion, the presence of one functional copy of the Lonp1 gene leads to impairment of mitochondrial ultrastructure and functions in vivo. |
