ArticlePLoS genetics2016
MPV17 Loss Causes Deoxynucleotide Insufficiency and Slow DNA Replication in Mitochondria.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04802707 (A Phase II, Monocenter, Single Arm Study To Assess The Safety and Efficacy Of Combination Deoxycytidine and Deoxythymidine For Mitochondrial Depletion Disorders), which is not on this map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II, Monocenter, Single Arm Study To Assess The Safety and Efficacy Of Combination Deoxycytidine and Deoxythymidine For Mitochondrial Depletion Disorders
Who cites it
53 citing papers in PubMed, 108 citations in OpenAlex.
- Bioinformatic analysis of differentially expressed mitochondrion-related genes, immune cell infiltration, and diagnostic value in Alzheimer's disease.BMC neurology · 2026Article
- Identification of novel candidate neural genes for diet-induced obesity in outbred heterogeneous stock rats.Research square · 2026Article
- Mitochondrial DNA replication is regulated by endoplasmic reticulum-mitochondrial contact sites, the mitochondrial calcium uniporter, and manganese.Nucleic acids research · 2026Article
- 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
- Mitochondrial function is impaired in long COVID patients.Annals of medicine · 2025Observational
- High tide or low tide: the transport and metabolism of mitochondrial nucleotides.The Biochemical journal · 2025Review
- Inner-mitochondrial membrane protein PfMPV17 is linked to P. falciparum in vitro resistance to the indoloquinolizidine alkaloid alstonine.The Journal of antimicrobial chemotherapy · 2025Article
- Overview of neuroimaging in primary mitochondrial disorders.Pediatric radiology · 2025Review
- Precision Prediction of Alzheimer's Disease: Integrating Mitochondrial Energy Metabolism and Immunological Insights.Journal of molecular neuroscience : MN · 2025Article
- Decoding the mitochondria without a code: mechanistic insights into mitochondrial DNA depletion syndromes.Journal of biosciences · 2024Review
- Red Flags in Primary Mitochondrial Diseases: What Should We Recognize?International journal of molecular sciences · 2023Review
- Article
- Drug Drop Test: How to Quickly Identify Potential Therapeutic Compounds for Mitochondrial Diseases Using YeastInternational journal of molecular sciences · 2023Review
- Mitofilin Heterozygote Mice Display an Increase in Myocardial Injury and Inflammation after Ischemia/Reperfusion.Antioxidants (Basel, Switzerland) · 2023Article
- Mitochondrial Metabolomics of Sym1-Depleted Yeast Cells Revealed Them to Be Lysine Auxotroph.Cells · 2023Article
- A Drosophila model of the neurological symptoms in Mpv17-related diseases.Scientific reports · 2022Article
- 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
- Mitochondrial DNA Instability in Mammalian Cells.Antioxidants & redox signaling · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 10 institutions in 5 countries.
Funding
Abstract
MPV17 is a mitochondrial inner membrane protein whose dysfunction causes mitochondrial DNA abnormalities and disease by an unknown mechanism. Perturbations of deoxynucleoside triphosphate (dNTP) pools are a recognized cause of mitochondrial genomic instability; therefore, we determined DNA copy number and dNTP levels in mitochondria of two models of MPV17 deficiency. In Mpv17 ablated mice, liver mitochondria showed substantial decreases in the levels of dGTP and dTTP and severe mitochondrial DNA depletion, whereas the dNTP pool was not significantly altered in kidney and brain mitochondria that had near normal levels of DNA. The shortage of mitochondrial dNTPs in Mpv17-/- liver slows the DNA replication in the organelle, as evidenced by the elevated level of replication intermediates. Quiescent fibroblasts of MPV17-mutant patients recapitulate key features of the primary affected tissue of the Mpv17-/- mice, displaying virtual absence of the protein, decreased dNTP levels and mitochondrial DNA depletion. Notably, the mitochondrial DNA loss in the patients' quiescent fibroblasts was prevented and rescued by deoxynucleoside supplementation. Thus, our study establishes dNTP insufficiency in the mitochondria as the cause of mitochondrial DNA depletion in MPV17 deficiency, and identifies deoxynucleoside supplementation as a potential therapeutic strategy for MPV17-related disease. Moreover, changes in the expression of factors involved in mitochondrial deoxynucleotide homeostasis indicate a remodeling of nucleotide metabolism in MPV17 disease models, which suggests mitochondria lacking functional MPV17 have a restricted purine mitochondrial salvage pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.