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- W4385295064 abstract "ABSTRACT Dominant optic atrophy is an optic neuropathy with varying clinical symptoms and progression. A severe disorder is associated with certain OPA1 mutations and includes additional symptoms for >20% of patients. This underscores the consequences of OPA1 mutations in different cellular populations, not only retinal ganglionic cells. We assessed the effects of OPA1 loss of function on oxidative metabolism and antioxidant defences using an RNA-silencing strategy in a human epithelial cell line. We observed a decrease in the mitochondrial respiratory chain complexes, associated with a reduction in aconitase activity related to an increase in reactive oxygen species (ROS) production. In response, the NRF2 (also known as NFE2L2) transcription factor was translocated into the nucleus and upregulated SOD1 and GSTP1. This study highlights the effects of OPA1 deficiency on oxidative metabolism in replicative cells, as already shown in neurons. It underlines a translational process to use cycling cells to circumvent and describe oxidative metabolism. Moreover, it paves the way to predict the evolution of dominant optic atrophy using mathematical models that consider mitochondrial ROS production and their detoxifying pathways." @default.
- W4385295064 created "2023-07-28" @default.
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- W4385295064 date "2023-09-01" @default.
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- W4385295064 title "OPA1 deficiency impacts oxidative metabolism in cycling cells: a translational approach for degenerative diseases" @default.
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- W4385295064 doi "https://doi.org/10.1242/dmm.050266" @default.
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