Journal article

OXPHOS bioenergetic compensation does not explain disease penetrance in Leber hereditary optic neuropathy

M Isabel G Lopez Sanchez, Nicole J Van Bergen, Lisa S Kearns, Mark Ziemann, Helena Liang, Alex W Hewitt, David A Mackey, Ian A Trounce



Leber hereditary optic neuropathy (LHON) is one of the most common primary mitochondrial diseases. It is caused by point mutations in mitochondrial DNA (mtDNA) genes and in some cases, it can result in irreversible vision loss, primarily in young men. It is currently unknown why LHON mutations affect only some carriers and whether bioenergetic compensation enables unaffected carriers to overcome mitochondrial impairment and preserve cellular function. Here, we conducted bioenergetic metabolic assays and RNA sequencing to address this question using male-only, age-matched, m.11778G > A lymphoblasts and primary fibroblasts from both unaffected carriers and affected individuals. Our work indica..

View full abstract


Funding Acknowledgements

We acknowledge the financial support provided by the Ophthalmic Research Institute of Australia (M.I.G.L.S., D.A.M. and I.A.T.), the Mito Foundation (M.I.G.L.S) and National Health and Medical Research Council (D.A.M, A.W.H. and I.A.T.). CERA receives Operational Infrastructure Support from the Victorian Government. We thank and acknowledge the Australian Genome Research Facility (AGRF) for high throughput sequencing, and the support it receives from the Commonwealth. We wish to thank Steven Ngo and Kendall Ward for their technical assistance in genotyping LHON cell lines.