Ferreira 2020 PLoS Genet
|Ferreira N, Andoniou CE, Perks KL, Ermer JA, Rudler DL, Rossetti G, Periyakaruppiah A, Wong JKY, Rackham O, Noakes PG, Degli-Esposti MA, Filipovska A (2020) Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease. PLoS Genet 16:e1008604.|
Abstract: The influence of environmental insults on the onset and progression of mitochondrial diseases is unknown. To evaluate the effects of infection on mitochondrial disease we used a mouse model of Leigh Syndrome, where a missense mutation in the Taco1 gene results in the loss of the translation activator of cytochrome c oxidase subunit I (TACO1) protein. The mutation leads to an isolated complex IV deficiency that mimics the disease pathology observed in human patients with TACO1 mutations. We infected Taco1 mutant and wild-type mice with a murine cytomegalovirus and show that a common viral infection exacerbates the complex IV deficiency in a tissue-specific manner. We identified changes in neuromuscular morphology and tissue-specific regulation of the mammalian target of rapamycin pathway in response to viral infection. Taken together, we report for the first time that a common stress condition, such as viral infection, can exacerbate mitochondrial dysfunction in a genetic model of mitochondrial disease.
Labels: MiParea: Respiration Pathology: Infectious Stress:Mitochondrial disease Organism: Mouse Tissue;cell: Liver Preparation: Isolated mitochondria Enzyme: Complex IV;cytochrome c oxidase
Coupling state: LEAK, OXPHOS, ET Pathway: N, ROX HRR: Oxygraph-2k