Sep 21, 2023

PNAS: Coenzyme Q10 trapping in mitochondrial complex I underlies Leber’s hereditary optic neuropathy

AUTHORS: Jack T. Fuller, III; Steven Barnes; Lorenzo A. Sadun; Pujan Ajmera; Anastassia N. Alexandrova; Alfredo A. Sadun

In the genetic disease Leber’s hereditary optic neuropathy, inheritance of a specific, single mitochondrial DNA mutation can produce the sudden onset of permanent blindness in first one and then the other eye usually in young adulthood. The mutation affects proteins in mitochondrial complex I that produce energy for retinal neuron activity, but the mechanism by which the mutation causes mitochondrial dysfunction is unclear. Computational biochemistry tools were used to compare molecular interactions in the mutated protein and showed that electron transfer to Coenzyme Q10 is massively slowed, creating conditions favorable for the production of cell-damaging reactive oxygen species, providing an explanation of how the mutation disrupts mitochondrial function, initiating a cascade that may lead to blindness.

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