Details

Autor(en) / Beteiligte

• Ferreira, Nicola
• Andoniou, Christopher E
• Perks, Kara L
• Ermer, Judith A
• Rudler, Danielle L
• Rossetti, Giulia
• Periyakaruppiah, Ambika
• Wong, Jamie K Y
• Rackham, Oliver
• Noakes, Peter G
• Degli-Esposti, Mariapia A
• Filipovska, Aleksandra
• Kozjak-Pavlovic, Vera

Titel

Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease

Ist Teil von

• PLoS genetics, 2020-03, Vol.16 (3), p.e1008604

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.