ArticleThe Journal of clinical investigation2020
PRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Variability of Clinical Phenotypes Caused by Isolated Defects of Mitochondrial ATP Synthase.Physiological research · 2024Pooled it
- Mitochondrial Complex V Dysfunction in Neurodegeneration: Secondary Bystander or Primary Driver?Brain sciences · 2026Review
- [Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Analysis of genetic risk factors for Leber hereditary optic neuropathy in the Polish population.Journal of applied genetics · 2026Article
- A multistage cost-effective strategy for the molecular diagnosis of unexplained vision loss patients: practice in inherited ocular fundus disease.Molecular genetics and genomics : MGG · 2026Article
- PRICKLE3 protects VANGL proteins from CK1-mediated phosphorylation and RNF43-mediated degradation.Communications biology · 2025Article
- [Pathogenic mechanisms of Leber hereditary optic neuropathy caused by m.3472T>C mutation].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Article
- Vitamin A treatment restores vision failures arising from Leber's hereditary optic neuropathy-linked mtDNA mutation.JCI insight · 2025Article
- Technological advances in the diagnosis and management of inherited optic neuropathies.Frontiers in neurology · 2025Review
- XPNPEP2 regulates angiogenesis via modulation of mitochondrial function through SLC25A6.Frontiers in cell and developmental biology · 2025Article
- Mutation of CRYAB encoding a conserved mitochondrial chaperone and antiapoptotic protein causes hereditary optic atrophy.JCI insight · 2024Article
- Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.International journal of molecular sciences · 2024Review
- Origins of tissue and cell-type specificity in mitochondrial DNA (mtDNA) disease.Human molecular genetics · 2024Review
- The role of prickle proteins in vertebrate development and pathology.Molecular and cellular biochemistry · 2024Review
- The Optic Nerve at Stake: Update on Environmental Factors Modulating Expression of Leber's Hereditary Optic Neuropathy.Biomedicines · 2024Review
- Progress in diagnosis and treatment of Leber's hereditary optic neuropathy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Leber's hereditary optic neuropathy: Update on the novel genes and therapeutic options.Journal of the Chinese Medical Association : JCMA · 2024Article
- Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations.Journal of biomedical science · 2023Review
- Mutational burden of XPNPEP3 leads to defects in mitochondrial complex I and cilia in NPHPL1.iScience · 2023Article
- Optimized allotopic expression of mitochondrial ND6 transgene restored complex I and apoptosis deficiencies caused by LHON-linked ND6 14484T > C mutation.Journal of biomedical science · 2023Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease. X-linked nuclear modifiers were proposed to modify the phenotypic manifestation of LHON-associated mitochondrial DNA (mtDNA) mutations. By whole-exome sequencing, we identified the X-linked LHON modifier (c.157C>T, p.Arg53Trp) in PRICKLE3 encoding a mitochondrial protein linked to biogenesis of ATPase in 3 Chinese families. All affected individuals carried both ND4 11778G>A and p.Arg53Trp mutations, while subjects bearing only a single mutation exhibited normal vision. The cells carrying the p.Arg53Trp mutation exhibited defective assembly, stability, and function of ATP synthase, verified by PRICKLE3-knockdown cells. Coimmunoprecipitation indicated the direct interaction of PRICKLE3 with ATP synthase via ATP8. Strikingly, cells bearing both p.Arg53Trp and m.11778G>A mutations displayed greater mitochondrial dysfunction than those carrying only a single mutation. This finding indicated that the p.Arg53Trp mutation acted in synergy with the m.11778G>A mutation and deteriorated mitochondrial dysfunctions necessary for the expression of LHON. Furthermore, we demonstrated that Prickle3-deficient mice exhibited pronounced ATPase deficiencies. Prickle3-knockout mice recapitulated LHON phenotypes with retinal deficiencies, including degeneration of retinal ganglion cells and abnormal vasculature. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutations and X-linked nuclear modifiers.
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