ArticleHuman molecular genetics2009
Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 105 citations in OpenAlex.
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations.Journal of advanced research · 2026Article
- Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
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- Modelling POLG mutations in mice unravels a critical role of POLγΒ in regulating phenotypic severity.Nature communications · 2025Article
- AbaComplex Enhances Mitochondrial Biogenesis and Adipose Tissue Browning: Implications for Obesity and Glucose Regulation.Foods (Basel, Switzerland) · 2024Article
- Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy.Cell & bioscience · 2024Article
- A Drosophila model of the neurological symptoms in Mpv17-related diseases.Scientific reports · 2022Article
- Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective.Pharmaceutics · 2022Review
- AAV-vector based gene therapy for mitochondrial disease: progress and future perspectives.Orphanet journal of rare diseases · 2022Review
- Review
- Loss of mpv17 affected early embryonic development via mitochondria dysfunction in zebrafish.Cell death discovery · 2021Article
- Autosomal recessive diseases among the Athabaskans of the southwestern United States: anthropological, medical, and scientific aspects.Journal of applied genetics · 2021Review
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile.Frontiers in cellular neuroscience · 2021Article
- Mitochondrial Regulation of Diabetic Kidney Disease.Frontiers in medicine · 2021Review
- Opa1 Overexpression Protects from Early-Onset Mpv17Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder.The Journal of clinical investigation · 2020Article
- Inner mitochondrial membrane protein MPV17 mutant mice display increased myocardial injury after ischemia/reperfusion.American journal of translational research · 2020Article
- Clinical and molecular characterization of three patients with Hepatocerebral form of mitochondrial DNA depletion syndrome: a case series.BMC medical genetics · 2019Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
In humans, MPV17 mutations are responsible for severe mitochondrial depletion syndrome, mainly affecting the liver and the nervous system. To gain insight into physiopathology of MPV17-related disease, we investigated an available Mpv17 knockout animal model. We found severe mtDNA depletion in liver and, albeit to a lesser extent, in skeletal muscle, whereas hardly any depletion was detected in brain and kidney, up to 1 year after birth. Mouse embryonic fibroblasts did show mtDNA depletion, but only after several culturing passages, or in a serumless culturing medium. In spite of severe mtDNA depletion, only moderate decrease in respiratory chain enzymatic activities, and mild cytoarchitectural alterations, were observed in the Mpv17(-/-) livers, but neither cirrhosis nor failure ever occurred in this organ at any age. The mtDNA transcription rate was markedly increased in liver, which could contribute to compensate the severe mtDNA depletion. This phenomenon was associated with specific downregulation of Mterf1, a negative modulator of mtDNA transcription. The most relevant clinical features involved skin, inner ear and kidney. The coat of the Mpv17(-/-) mice turned gray early in adulthood, and 18-month or older mice developed focal segmental glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of cochlear sensory epithelia was reported as well. These symptoms were associated with significantly shorter lifespan. Coincidental with the onset of FSGS, there was hardly any mtDNA left in the glomerular tufts. These results demonstrate that Mpv17 controls mtDNA copy number by a highly tissue- and possibly cytotype-specific mechanism.
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Registered trials
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