ArticleThe Journal of clinical investigation2020
SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder.
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 61 papers.
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Who cites it
61 citing papers in PubMed, 91 citations in OpenAlex.
- Biomarker profiles in idiopathic and progressive pulmonary fibrosis after LPARespiratory research · 2026Trial
- Structural and single-molecule insights into the core human mitochondrial DNA replisome.The Biochemical journal · 2026Review
- Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- Mitochondrial transplantation restores mitochondrial content and function in SSBP1-related mitochondrial DNA depletion syndrome.BMB reports · 2026Article
- Exome Sequencing in a Large Cohort with Ciliopathy-Related Kidney Disease.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- An unbiased proteomic platform for ATE1-based arginylation profiling.Nature chemical biology · 2025Article
- Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Morpholino Knockdown in Zebrafish: A Tool to Investigate the Functional Impact of Variants of Unknown Significance in Mitochondrial Diseases.Neuromolecular medicine · 2025Review
- SSBP1 is a prognostic biomarker and promotes the progression of lung adenocarcinoma via p53 signaling pathway.Discover oncology · 2025Article
- Review
- A case with bilateral C-shaped autofluorescence in retinal degeneration.American journal of ophthalmology case reports · 2025Article
- Article
- Deoxynucleoside supplementation ameliorates the disease associated phenotypes in a zebrafish model of RRM2B mtDNA depletion syndrome.Human molecular genetics · 2025Article
- Clinical and genetic landscape of optic atrophy in 826 families: insights from 50 nuclear genes.Brain : a journal of neurology · 2025Article
- A novel m.5906G > a variant in MT-CO1 causes MELAS/Leigh overlap syndrome.Molecular genetics and genomics : MGG · 2024Article
- Structures of the mitochondrial single-stranded DNA binding protein with DNA and DNA polymerase γ.Nucleic acids research · 2024Article
- Discovery of novel disease-causing mutation inMolecular therapy. Nucleic acids · 2024Article
- Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.International journal of molecular sciences · 2024Review
- The mutation R107Q alters mtSSB ssDNA compaction ability and binding dynamics.Nucleic acids research · 2024Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
47 authors at 17 institutions in 8 countries.
Funding
Abstract
Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect the amount of SSBP1 protein and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids, and 7S-DNA amounts as well as mtDNA replication, affecting replisome machinery. The variable mtDNA depletion in cells was reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits, and complex amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex vivo in biopsies of affected tissues, such as kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by WT mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as a cause of human pathology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.