ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
AAV-mediated liver-specific MPV17 expression restores mtDNA levels and prevents diet-induced liver failure.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
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- Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Gene therapy prevents hepatic mitochondrial dysfunction in murine deoxyguanosine kinase deficiency.Molecular therapy. Methods & clinical development · 2025Article
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
- Restoration of defective oxidative phosphorylation to a subset of neurons prevents mitochondrial encephalopathy.EMBO molecular medicine · 2024Article
- Liver transplantation for mitochondrial DNA depletion syndrome caused byFrontiers in surgery · 2024Article
- Drug Drop Test: How to Quickly Identify Potential Therapeutic Compounds for Mitochondrial Diseases Using YeastInternational journal of molecular sciences · 2023Review
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- Gene therapy for primary mitochondrial diseases: experimental advances and clinical challenges.Nature reviews. Neurology · 2022Review
- Double administration of self-complementary AAV9NDUFS4 prevents Leigh disease in Ndufs4-/- mice.Brain : a journal of neurology · 2022Article
- Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective.Pharmaceutics · 2022Review
- Mitochondrial Membranes and Mitochondrial Genome: Interactions and Clinical Syndromes.Membranes · 2022Review
- AAV-vector based gene therapy for mitochondrial disease: progress and future perspectives.Orphanet journal of rare diseases · 2022Review
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- A Yeast-Based Repurposing Approach for the Treatment of Mitochondrial DNA Depletion Syndromes Led to the Identification of Molecules Able to Modulate the dNTP Pool.International journal of molecular sciences · 2021Article
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Moving towards clinical trials for mitochondrial diseases.Journal of inherited metabolic disease · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in human MPV17 cause a hepatocerebral form of mitochondrial DNA depletion syndrome (MDS) hallmarked by early-onset liver failure, leading to premature death. Liver transplantation and frequent feeding using slow-release carbohydrates are the only available therapies, although surviving patients eventually develop slowly progressive peripheral and central neuropathy. The physiological role of Mpv17, including its functional link to mitochondrial DNA (mtDNA) maintenance, is still unclear. We show here that Mpv17 is part of a high molecular weight complex of unknown composition, which is essential for mtDNA maintenance in critical tissues, i.e. liver, of a Mpv17 knockout mouse model. On a standard diet, Mpv17-/- mouse shows hardly any symptom of liver dysfunction, but a ketogenic diet (KD) leads these animals to liver cirrhosis and failure. However, when expression of human MPV17 is carried out by adeno-associated virus (AAV)-mediated gene replacement, the Mpv17 knockout mice are able to reconstitute the Mpv17-containing supramolecular complex, restore liver mtDNA copy number and oxidative phosphorylation (OXPHOS) proficiency, and prevent liver failure induced by the KD. These results open new therapeutic perspectives for the treatment of MPV17-related liver-specific MDS.
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