Affinage

MPV17

Mitochondrial inner membrane protein Mpv17 · UniProt P39210

Length
176 aa
Mass
19.7 kDa
Annotated
2026-06-10
89 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MPV17 is an inner mitochondrial membrane protein required for mitochondrial DNA maintenance, the loss of which causes oxidative phosphorylation failure and mtDNA depletion in patients and knockout mice (PMID:16582910). Its mitochondrial localization and conserved function are established by the yeast ortholog SYM1, which resides in the inner membrane and is complemented by mammalian Mpv17 (PMID:15189984), and by cell-autonomous requirement in zebrafish mitochondria (PMID:23862018). Reconstituted MPV17 forms a non-selective, weakly cation-selective channel (~1.8 nm pore) whose gating is voltage-, redox-, and pH-dependent (PMID:25861990); structurally it is a compact six-helix membrane protein that assembles into disulfide-stabilized oligomers, and disease mutations abolish this oligomerization (PMID:34116124). The functional unit is a high-molecular-weight complex whose reassembly upon MPV17 re-expression restores mtDNA copy number and OXPHOS (PMID:24247928), and pathological mutations disrupt this complex even when the protein localizes correctly (PMID:30273399). The core mechanism linking the channel to mtDNA maintenance is control of the mitochondrial deoxynucleotide supply: MPV17 deficiency causes tissue-specific depletion of dGTP and dTTP pools, slowing mtDNA replication, with deoxynucleoside supplementation rescuing depletion in patient cells (PMID:26760297), and is associated with aberrant ribonucleotide (rGMP) and uracil incorporation into mtDNA (PMID:29106596, PMID:30385507); the Drosophila channel translocates uridine, and pyrimidine-precursor (orotic acid) supplementation rescues mtDNA content in zebrafish (PMID:30833296, PMID:37810222). Beyond nucleotide supply, MPV17 modulates mitochondrial membrane potential, ROS, and cristae integrity, with Opa1-dependent cristae stabilization being epistatically protective against apoptosis in MPV17 loss (PMID:25861990, PMID:32562616). MPV17 deficiency drives tissue-specific pathology and cell-death programs in kidney, cochlea, and hair cells through elevated ROS and mitochondrial dysfunction (PMID:24598802, PMID:22322422, PMID:34413725).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 Medium

    The first mechanistic question was where Mpv17 acts and how it relates to reactive oxygen metabolism; gain- and loss-of-function pointed to a role in ROS production, initially assigned to peroxisomes.

    Evidence Subcellular fractionation and transfection ROS assays in mouse cells

    PMID:7957077

    Open questions at the time
    • Localization later reassigned to mitochondria
    • ROS effect mechanism not defined
  2. 1998 Medium

    Early loss-of-function work linked Mpv17 absence to a defined downstream molecular readout, establishing an inverse causal relationship with MMP-2 expression in affected tissues.

    Evidence In situ/RT-PCR of Mpv17-/- tissues with transfection rescue measuring MMP-2

    PMID:9658163

    Open questions at the time
    • Mechanism connecting Mpv17 to MMP-2 unknown
    • Relationship to mitochondrial function not established
  3. 2004 High

    To resolve the organelle of action, the yeast ortholog SYM1 was localized and tested functionally, establishing inner mitochondrial membrane residence and cross-species functional conservation.

    Evidence GFP-tagging and genetic complementation of sym1Δ by mammalian Mpv17

    PMID:15189984

    Open questions at the time
    • Molecular activity still undefined
    • Substrate/transport function not addressed
  4. 2006 High

    Whether MPV17 acts in mitochondria in humans and what its loss causes was settled by correcting the localization and linking deficiency to mtDNA depletion and OXPHOS failure in patients and mice.

    Evidence Subcellular localization, patient mutation analysis, Mpv17-/- mouse phenotyping

    PMID:16582910

    Open questions at the time
    • Molecular mechanism of mtDNA depletion not yet known
    • No biochemical activity assigned
  5. 2013 High

    The physical form of MPV17's function was identified as a high-molecular-weight mitochondrial complex required for mtDNA maintenance, with in vivo re-expression reconstituting it.

    Evidence AAV liver-specific re-expression, blue-native PAGE, mtDNA and OXPHOS readouts; plus zebrafish cell-autonomy/localization

    PMID:23862018 PMID:24247928

    Open questions at the time
    • Composition of the complex unknown
    • How complex maintains mtDNA unresolved
  6. 2015 High

    The molecular activity question was answered by reconstitution: MPV17 forms a non-selective channel whose gating is redox/pH/voltage- and phosphorylation-sensitive, connecting it to membrane potential and ROS control.

    Evidence Planar lipid bilayer electrophysiology, phosphomimetic mutagenesis, ΔΨm/ROS measurement in KO fibroblasts

    PMID:25861990

    Open questions at the time
    • Physiological permeant species not identified in this study
    • Link between channel activity and mtDNA maintenance not yet mechanistic
  7. 2016 High

    The mechanism connecting MPV17 to mtDNA depletion was established as tissue-specific mitochondrial dNTP insufficiency, with deoxynucleoside rescue proving causality.

    Evidence HPLC dNTP pool measurement, replication intermediate analysis, deoxynucleoside rescue in patient fibroblasts

    PMID:26760297

    Open questions at the time
    • Whether MPV17 directly transports dNTP precursors not shown
    • Basis of tissue specificity unresolved
  8. 2017 High

    Building on the dNTP model, ribonucleotide mapping showed MPV17 loss alters mtDNA quality (rGMP incorporation) tissue-specifically, refining its role to controlling local dGTP availability/quality for replication.

    Evidence HydEn-seq rNMP mapping plus dNTP pools across tissues in Mpv17-/- mice

    PMID:29106596

    Open questions at the time
    • Mechanism of tissue-divergent outcomes (depletion vs deletions) unclear
    • Direct substrate not defined
  9. 2018 Medium

    The specific transported species was probed metabolically and structurally: MPV17 was implicated in dTMP/folate delivery preventing uracil incorporation, and disease mutations were shown to disrupt complex assembly rather than localization.

    Evidence MPV17 knockdown with folate/uracil/dTMP-pathway assays; yeast SYM1 disease-allele native PAGE complex analysis

    PMID:30273399 PMID:30385507

    Open questions at the time
    • Transporter function inferred, not reconstituted
    • Direct substrate identity remained uncertain
  10. 2019 High

    An in vivo model linked MPV17 loss to impaired pyrimidine de novo synthesis, with a precursor rescue establishing the pyrimidine pathway as functionally downstream.

    Evidence Zebrafish mpv17 KO with EM, DHODH activity, orotic acid rescue, mtDNA quantification

    PMID:30833296

    Open questions at the time
    • Whether DHODH deficit is direct or secondary unclear
    • Connection to channel activity not made
  11. 2021 High

    Structure and oligomerization were resolved, defining MPV17 as a six-helix protein whose disulfide-stabilized oligomeric assembly is required for function and abolished by disease variants, and patient cells showed mutation-specific destabilization and mislocalization.

    Evidence NMR, nanodisc reconstitution, cysteine mutagenesis; patient cell stability/respiration/ΔΨm/localization assays

    PMID:33815063 PMID:34116124

    Open questions at the time
    • High-resolution oligomeric pore structure not determined
    • Trigger for oligomerization in vivo unconfirmed
  12. 2023 High

    Direct evidence for metabolite transport was obtained: the Drosophila channel translocates uridine but not orotate, tying channel activity to nucleotide precursor supply, while metabolic remodeling and mtDNA depletion confirmed in vivo consequences.

    Evidence Bilayer electrophysiology with uridine/orotate translocation, Drosophila KO metabolomics and mtDNA quantification

    PMID:37810222

    Open questions at the time
    • Whether human MPV17 transports the same species not directly shown
    • Full permeant spectrum undefined
  13. 2024 Medium

    Additional protective functions were identified: MPV17 stabilizes the mitochondrial glutathione transporter SLC25A10 to preserve GSH and prevent ferroptosis, and is a transcriptional target of Nrf2, and interacts with cristae/calcium-handling proteins.

    Evidence MPV17 overexpression, SLC25A10 ubiquitination/GSH/ferroptosis assays, Nrf2 ChIP/reporter; cardiac Co-IP/MS and calcium retention assays

    PMID:32774709 PMID:39409161

    Open questions at the time
    • Co-IP partners (ATP synthase, MIC60, CypD, GRP75) lack reciprocal validation
    • Direct vs indirect SLC25A10 stabilization mechanism unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single non-selective channel produces opposing, tissue-specific cell-fate outcomes (anti-apoptotic in kidney/cochlea versus pro-apoptotic in β-cells) and which permeant species the human protein physiologically transports remain unresolved.
  • Human channel substrate not directly demonstrated
  • Mechanistic basis of cell-type-specific pro- vs anti-apoptotic roles unknown
  • Composition of the high-MW complex undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0005198 structural molecule activity 2 GO:0140313 molecular sequestering activity 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-69306 DNA Replication 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ATP SYNTHASEHSPA9MIC60OPA1PPIFSLC25A10
Complex memberships
MPV17 high-molecular-weight inner mitochondrial membrane complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 MPV17 encodes an inner mitochondrial membrane protein (not peroxisomal as previously claimed); its absence causes oxidative phosphorylation failure and mtDNA depletion in affected human patients and Mpv17-/- mice. Subcellular fractionation/localization, patient mutation analysis, functional characterization in Mpv17-/- mouse model Nature genetics High 16582910
1994 The mouse Mpv17 gene product localizes to peroxisomes (early claim, later revised for human MPV17); its loss reduces intracellular ROS production, while overexpression dramatically enhances ROS levels, indicating direct involvement in peroxisomal reactive oxygen metabolism. Subcellular fractionation, transfection overexpression assay measuring intracellular ROS The EMBO journal Medium 7957077
2004 The yeast ortholog of MPV17, SYM1, localizes to the inner mitochondrial membrane (not peroxisomes); expression of mammalian Mpv17 in sym1Δ cells complements the 37°C ethanol growth defect, demonstrating functional orthology and mitochondrial localization. GFP-tagging localization, genetic complementation assay Eukaryotic cell High 15189984
2009 The yeast Sym1 (MPV17 ortholog) is essential for maintaining OXPHOS, glycogen storage, mitochondrial morphology, and mtDNA stability under stress; multicopy suppressor and metabolic suppressor studies show metabolic impairment and mtDNA instability occur independently upon SYM1 ablation, and Sym1 loss causes flattening of mitochondrial cristae, suggesting a structural role for the inner mitochondrial membrane. Yeast genetics (KO, multicopy suppressor screen), electron microscopy of mitochondria, metabolic assays Human molecular genetics High 20042463
2015 Recombinant human MPV17 reconstituted in planar lipid bilayers forms a non-selective, weakly cation-selective channel with a pore diameter of ~1.8 nm; channel gating is voltage-dependent and regulated by redox conditions and pH; phosphomimetic mutations affect gating; Mpv17-/- embryonic fibroblasts show elevated mitochondrial membrane potential (ΔΨm) and increased ROS, and deficient mitochondria display accelerated fission. Electrophysiology (planar lipid bilayer reconstitution), site-directed mutagenesis of phosphorylation-mimicking residues, mitochondrial membrane potential measurement in Mpv17-/- fibroblasts The Journal of biological chemistry High 25861990
2016 MPV17 deficiency causes tissue-specific depletion of mitochondrial dGTP and dTTP pools, slowing mtDNA replication (evidenced by elevated replication intermediates); deoxynucleoside supplementation prevented and rescued mtDNA depletion in patient fibroblasts, establishing mitochondrial dNTP insufficiency as the mechanism of mtDNA depletion in MPV17 disease. dNTP pool measurement by HPLC in Mpv17-/- mouse liver, replication intermediate analysis, deoxynucleoside rescue experiments in patient quiescent fibroblasts PLoS genetics High 26760297
2013 Mpv17 is part of a high molecular weight complex of unknown composition in mitochondria that is essential for mtDNA maintenance in liver; AAV-mediated liver-specific re-expression of human MPV17 in Mpv17-/- mice reconstitutes this supramolecular complex, restores mtDNA copy number and OXPHOS proficiency, and prevents ketogenic diet-induced liver failure. AAV gene delivery, native gel/blue-native PAGE detection of high-MW complex, mtDNA quantification, OXPHOS activity assays Molecular therapy High 24247928
2017 In Mpv17-/- mouse mtDNA, the pattern of embedded ribonucleotides is altered, with a marked increase in rGMPs in liver mtDNA, while brain shows no overall dGTP pool change; aberrant rGMP incorporation is associated with early-onset mtDNA depletion in liver and late-onset multiple deletions in brain, suggesting Mpv17 controls the local concentration or quality of dGTP available to the replication machinery. Ribonucleotide mapping in mtDNA (HydEn-seq), dNTP pool measurements, tissue-specific analysis in Mpv17-/- mice Nucleic acids research High 29106596
2018 Reduced MPV17 expression in HeLa cells decreases mitochondrial folate levels by 43% and increases uracil incorporation into mtDNA by 3-fold, without changing mitochondrial de novo or salvage dTMP biosynthetic capacity, indicating MPV17 may function as a transporter delivering cytosolic dTMP to mitochondria. MPV17 siRNA knockdown, mitochondrial folate measurement, uracil quantification in mtDNA, dTMP pathway enzyme activity assays The Journal of biological chemistry Medium 30385507
2021 NMR structural analysis shows refolded MPV17 in detergent micelles adopts a compact structure with six membrane-embedded α-helices; MPV17 forms disulfide bridge-stabilized oligomers in lipid bilayers, and disease-linked mutations abolish oligomerization, suggesting that oxidative stress-induced oligomeric pore formation may be required for metabolite transport. NMR spectroscopy, biophysical oligomerization assays, lipid nanodisc reconstitution, cysteine mutagenesis, disease-variant functional testing Journal of molecular biology High 34116124
2018 Pathological MPV17 missense mutations modeled in yeast SYM1 all disrupt formation of the high molecular weight complex previously identified in yeast and mammalian tissues, even when the mutant proteins correctly localize to mitochondria and most are stable, indicating that complex assembly is the critical functional unit disrupted by disease mutations. Yeast mutagenesis, mitochondrial fractionation, native PAGE/blue-native PAGE complex analysis, protein localization and stability assays PloS one High 30273399
2019 Zebrafish mpv17 null mutants show early severe ultrastructural mitochondrial alterations in liver with impaired respiratory chain function and activation of mitochondrial quality control; mpv17 KO larvae have impaired dihydroorotate dehydrogenase (DHODH) activity, and supplementation with orotic acid (pyrimidine precursor) rescues both iridophore number and mtDNA content, linking Mpv17 loss to impaired pyrimidine de novo synthesis. Zebrafish mpv17 KO (CRISPR), electron microscopy of liver mitochondria, respiratory chain assays, DHODH activity assay, orotic acid rescue experiment, mtDNA quantification Disease models & mechanisms High 30833296
2023 Drosophila Mpv17 (dMpv17) forms an ion channel in planar lipid bilayers with electrophysiological properties affected by pathological mutations; the reconstituted channel translocates uridine but not orotate across the membrane; dMpv17 KO flies show profound mtDNA depletion in fat body, increased glycolytic flux, upregulation of glycogenolysis/glycolysis genes, and reduced lifespan under starvation. Planar lipid bilayer electrophysiology, uridine/orotate translocation assay, Drosophila KO (genetics), mtDNA quantification, metabolomics/gene expression iScience High 37810222
2020 Immunoprecipitation followed by mass spectrometry identified ATP synthase, Cyclophilin D, MIC60, and GRP75 as proteins interacting with MPV17 in cardiac mitochondria; this interaction is reduced after ischemia/reperfusion, and MPV17 mutant mice show compromised calcium retention capacity in mitochondria after I/R, suggesting MPV17 maintains mitochondrial cristae organization and calcium handling. Co-immunoprecipitation, mass spectrometry, calcium retention capacity assay in isolated heart mitochondria from Mpv17 mutant mice American journal of translational research Medium 32774709
2024 MPV17 maintains mitochondrial glutathione levels by stabilizing SLC25A10 (the mitochondrial inner-membrane glutathione transporter) against ubiquitination-dependent degradation; MPV17 overexpression prevents SLC25A10 protein loss under iron overload, thereby preserving mitochondrial GSH import and protecting cardiomyocytes from ferroptosis. MPV17 is a transcriptional target of Nrf2. Adenovirus-mediated MPV17 overexpression, SLC25A10 ubiquitination assay, mitochondrial glutathione measurement, ferroptosis markers, Nrf2 ChIP/luciferase reporter International journal of molecular sciences Medium 39409161
1998 Loss of the Mpv17 gene product causes a strong upregulation of matrix metalloproteinase-2 (MMP-2) expression in kidney, cochlea, and tissue-culture fibroblasts; transfection of human MPV17 into Mpv17-negative cells establishes an inverse causal relationship between Mpv17 and MMP-2 expression. In situ hybridization/RT-PCR of Mpv17-/- tissues, transfection rescue experiment measuring MMP-2 expression Molecular biology of the cell Medium 9658163
1999 Glomerular damage in Mpv17-/- mice is caused by overproduction of oxygen radicals and lipid peroxidation; antioxidant treatment with radical scavengers (dithiomethylurea, probucol) inhibited glomerular disease development and preserved glomerular polyanion, while steroid treatment had no effect. In vivo pharmacological intervention in Mpv17-/- mice, ROS/lipid peroxidation measurement in isolated glomeruli, proteinuria assessment The American journal of pathology Medium 10233845
2014 Mpv17 localizes to mitochondria of podocytes; Mpv17 deficiency in podocytes leads to increased mitochondrial ROS, oxidative DNA damage, reduced mtDNA content, altered mitochondrial configuration, and increased susceptibility to apoptosis under oxidative stress in vitro and increased proteinuria and renal insufficiency in nephrotoxic serum nephritis in vivo. Immunofluorescence localization, Mpv17-/- mouse nephritis model (in vivo), podocyte cell culture loss-of-function (in vitro) with mitochondrial functional assays American journal of physiology. Renal physiology High 24598802
2013 In zebrafish, mpv17 (transparent/tra locus) acts cell-autonomously in iridophores as shown by cell transplantation experiments; the Mpv17 protein localizes to mitochondria; iridophore death is the primary phenotype, with secondary reduction of melanophores as a consequence of iridophore loss. Cell transplantation, fluorescence localization in zebrafish, genetic deletion analysis Biology open High 23862018
2021 MPV17 mutations destabilize the protein, leading to reduced MPV17 levels; different mutations cause distinct cellular abnormalities including increased ROS, decreased oxygen consumption, loss of mitochondrial membrane potential (ΔΨm), and mislocalization of the MPV17 protein from mitochondria. Patient-derived cell lines with MPV17 KD/mutation, Western blot for protein stability, mitochondrial respiration (Seahorse), ROS measurement, ΔΨm assay, immunofluorescence localization Frontiers in cellular neuroscience Medium 33815063
2020 Opa1 overexpression in Mpv17-/- mice protects from kidney disease and partially restores mtDNA content and OXPHOS activities; the protective mechanism is a block in apoptosis mediated by stabilization of mitochondrial cristae, establishing epistatic relationship between Mpv17 and Opa1-dependent cristae integrity. Genetic epistasis (Mpv17-/- × Opa1tg double mutant), mtDNA quantification, OXPHOS activity assays, electron microscopy of mitochondrial cristae, apoptosis assays Molecular therapy High 32562616
2012 Loss of Mpv17 function in Mpv17-/- mouse cochlea initiates tissue-specific cell-death pathways: outer hair cells undergo paraptosis-like death (vacuolization, lysis), while melanocyte-like intermediate cells of the stria vascularis undergo apoptosis, demonstrating that mitochondrial Mpv17 absence triggers distinct cell-type-specific death programs. Electron microscopy of Mpv17-/- cochlear tissue at defined developmental ages, ultrastructural analysis of cell death morphology Cell and tissue research Medium 22322422
2021 In zebrafish mpv17 mutant hair cells, mitochondria show elevated ROS, elevated calcium, hyperpolarized transmembrane potential, and greater vulnerability to neomycin, indicating impaired mitochondrial homeostasis; Mpv17 functions as a non-selective cation channel maintaining mitochondrial homeostasis in hair cells. Live imaging of mitochondrial ROS, calcium, and membrane potential in zebrafish lateral line hair cells; neomycin susceptibility assay; synapse morphology analysis Frontiers in cellular neuroscience Medium 34413725
2023 MPV17 expression in pancreatic β-cells promotes apoptosis (proapoptotic role): Mpv17-deficient mice are resistant to streptozotocin- and Ins2Akita-induced diabetes with significantly less β-cell apoptosis; MPV17 knockdown in MIN6 cells improves viability and prevents caspase-3 activation under STZ or palmitic acid stress, contrasting with its anti-apoptotic role in other cell types. In vivo STZ and Ins2Akita diabetes models in Mpv17-/- mice, β-cell apoptosis quantification, MIN6 cell MPV17 knockdown with STZ/PA challenge, caspase-3 activation assay Clinical science Medium 37522959

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nature genetics 342 16582910
2006 Navajo neurohepatopathy is caused by a mutation in the MPV17 gene. American journal of human genetics 122 16909392
2007 Mutations in the MPV17 gene are responsible for rapidly progressive liver failure in infancy. Hepatology (Baltimore, Md.) 96 17694548
1994 The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species. The EMBO journal 93 7957077
1999 Glomerular overproduction of oxygen radicals in Mpv17 gene-inactivated mice causes podocyte foot process flattening and proteinuria: A model of steroid-resistant nephrosis sensitive to radical scavenger therapy. The American journal of pathology 85 10233845
2013 transparent, a gene affecting stripe formation in Zebrafish, encodes the mitochondrial protein Mpv17 that is required for iridophore survival. Biology open 74 23862018
2017 A defect in the mitochondrial protein Mpv17 underlies the transparent casper zebrafish. Developmental biology 73 28760346
2016 MPV17 Loss Causes Deoxynucleotide Insufficiency and Slow DNA Replication in Mitochondria. PLoS genetics 68 26760297
2009 MPV17-associated hepatocerebral mitochondrial DNA depletion syndrome: new patients and novel mutations. Molecular genetics and metabolism 68 20074988
2009 Sym1, the yeast ortholog of the MPV17 human disease protein, is a stress-induced bioenergetic and morphogenetic mitochondrial modulator. Human molecular genetics 64 20042463
2012 MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions. Archives of neurology 60 22964873
2015 The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential. The Journal of biological chemistry 58 25861990
2014 Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro. American journal of physiology. Renal physiology 53 24598802
2012 MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle. Neuromuscular disorders : NMD 53 22508010
2008 Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations. Archives of neurology 52 18695062
2013 Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene. European journal of human genetics : EJHG 48 23714749
2018 MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects. Human mutation 47 29282788
2004 SYM1 is the stress-induced Saccharomyces cerevisiae ortholog of the mammalian kidney disease gene Mpv17 and is required for ethanol metabolism and tolerance during heat shock. Eukaryotic cell 46 15189984
2013 AAV-mediated liver-specific MPV17 expression restores mtDNA levels and prevents diet-induced liver failure. Molecular therapy : the journal of the American Society of Gene Therapy 45 24247928
2008 Lethal hepatopathy and leukodystrophy caused by a novel mutation in MPV17 gene: description of an alternative MPV17 spliced form. Molecular genetics and metabolism 39 18329934
2002 M-LP, Mpv17-like protein, has a peroxisomal membrane targeting signal comprising a transmembrane domain and a positively charged loop and up-regulates expression of the manganese superoxide dismutase gene. The Journal of biological chemistry 38 12471025
2008 Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients. Journal of hepatology 36 19012992
2017 Aberrant ribonucleotide incorporation and multiple deletions in mitochondrial DNA of the murine MPV17 disease model. Nucleic acids research 35 29106596
2018 The mitochondrial inner membrane protein MPV17 prevents uracil accumulation in mitochondrial DNA. The Journal of biological chemistry 34 30385507
2006 Human Mpv17-like protein is localized in peroxisomes and regulates expression of antioxidant enzymes. Biochemical and biophysical research communications 33 16631601
2009 Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II. Molecular genetics and metabolism 32 19520594
1996 Inner ear defect similar to Alport's syndrome in the glomerulosclerosis mouse model Mpv17. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 32 9044568
2015 The role of the Mpv17 protein mutations of which cause mitochondrial DNA depletion syndrome (MDDS): lessons from homologs in different species. Biological chemistry 27 25205723
2001 Cloning, mapping, genomic organization, and expression of mouse M-LP, a new member of the peroxisomal membrane protein Mpv17 domain family. Biochemical and biophysical research communications 27 11327696
2005 Abnormal basement membrane in the inner ear and the kidney of the Mpv17-/- mouse strain: ultrastructural and immunohistochemical investigations. Histochemistry and cell biology 24 16041630
1998 Expression of the recessive glomerulosclerosis gene Mpv17 regulates MMP-2 expression in fibroblasts, the kidney, and the inner ear of mice. Molecular biology of the cell 24 9658163
2019 The zebrafish orthologue of the human hepatocerebral disease gene MPV17 plays pleiotropic roles in mitochondria. Disease models & mechanisms 22 30833296
1993 The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization. Human molecular genetics 22 8281143
2000 Course of renal injury in the Mpv17-deficient transgenic mouse. Journal of the American Society of Nephrology : JASN 21 10820170
1997 Loss of auditory function in transgenic Mpv17-deficient mice. Hearing research 21 9447939
2012 Hepatocerebral form of mitochondrial DNA depletion syndrome due to mutation in MPV17 gene. Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 19 22824774
2016 MPV17 mutations in patients with hepatocerebral mitochondrial DNA depletion syndrome. Molecular genetics and metabolism reports 18 27536553
2015 A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy. BMC neurology 18 26437932
2005 A novel alternative spliced Mpv17-like protein isoform localizes in cytosol and is expressed in a kidney- and adult-specific manner. Experimental cell research 18 15541722
2021 MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile. Frontiers in cellular neuroscience 16 33815063
2018 MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy. Clinical genetics 16 30298599
2012 Missing mitochondrial Mpv17 gene function induces tissue-specific cell-death pathway in the degenerating inner ear. Cell and tissue research 16 22322422
1995 Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by transgenesis with the human Mpv17 homologue. Kidney international 15 7564095
2021 Influence of Mpv17 on Hair-Cell Mitochondrial Homeostasis, Synapse Integrity, and Vulnerability to Damage in the Zebrafish Lateral Line. Frontiers in cellular neuroscience 14 34413725
2020 Opa1 Overexpression Protects from Early-Onset Mpv17-/--Related Mouse Kidney Disease. Molecular therapy : the journal of the American Society of Gene Therapy 14 32562616
2001 Enhanced gamma-glutamyl transpeptidase expression and superoxide production in Mpv17-/- glomerulosclerosis mice. Biological chemistry 14 11530932
2018 Identification of a single MPV17 nonsense-associated altered splice variant in 24 South African infants with mitochondrial neurohepatopathy. Clinical genetics 13 29318572
2008 Lack of founder effect for an identical mtDNA depletion syndrome (MDS)-associated MPV17 mutation shared by Navajos and Italians. Neuromuscular disorders : NMD 13 18261905
2023 Mitochondrial protein MPV17 promotes β-cell apoptosis in diabetogenesis. Clinical science (London, England : 1979) 12 37522959
2021 NMR Structural and Biophysical Analysis of the Disease-Linked Inner Mitochondrial Membrane Protein MPV17. Journal of molecular biology 12 34116124
2018 Pathological alleles of MPV17 modeled in the yeast Saccharomyces cerevisiae orthologous gene SYM1 reveal their inability to take part in a high molecular weight complex. PloS one 12 30273399
2013 Adult-Onset Fatal Neurohepatopathy in a Woman Caused by MPV17 Mutation. JIMD reports 12 24190800
2023 Novel Variants in MPV17, PRX, GJB1, and SACS Cause Charcot-Marie-Tooth and Spastic Ataxia of Charlevoix-Saguenay Type Diseases. Genes 11 36833258
2021 Loss of mpv17 affected early embryonic development via mitochondria dysfunction in zebrafish. Cell death discovery 11 34537814
2012 Identification of Rhit as a novel transcriptional repressor of human Mpv17-like protein with a mitigating effect on mitochondrial dysfunction, and its transcriptional regulation by FOXD3 and GABP. Free radical biology & medicine 11 22306510
2020 Inner mitochondrial membrane protein MPV17 mutant mice display increased myocardial injury after ischemia/reperfusion. American journal of translational research 10 32774709
2015 Identification of interacting partners of Human Mpv17-like protein with a mitigating effect of mitochondrial dysfunction through mtDNA damage. Free radical biology & medicine 10 26165189
2015 Increased Expression of Mitochondrial Inner-Membrane Protein Mpv17 After Intracerebral Hemorrhage in Adult Rats. Neurochemical research 9 26123482
1999 Age-dependent hypertension in Mpv17-deficient mice, a transgenic model of glomerulosclerosis and inner ear disease. Experimental gerontology 9 10673153
2024 MPV17 Prevents Myocardial Ferroptosis and Ischemic Cardiac Injury through Maintaining SLC25A10-Mediated Mitochondrial Glutathione Import. International journal of molecular sciences 7 39409161
2023 Drosophila Mpv17 forms an ion channel and regulates energy metabolism. iScience 7 37810222
2001 Ultrastructural and physiological defects in the cochlea of the Mpv17 mouse strain. A comparison between young and old adult animals. Hearing research 7 11377883
2018 Knockout of Mpv17-Like Protein (M-LPH) Gene in Human Hepatoma Cells Results in Impairment of mtDNA Integrity through Reduction of TFAM, OGG1, and LIG3 at the Protein Levels. Oxidative medicine and cellular longevity 6 30310528
2010 A novel transcriptional repressor, Rhit, is involved in heat-inducible and age-dependent expression of Mpv17-like protein, a participant in reactive oxygen species metabolism. Molecular and cellular biology 6 20231359
2020 Human Mpv17-like protein with a mitigating effect on mtDNA damage is involved in cAMP/PKA signaling in the mitochondrial matrix. Biochimica et biophysica acta. Molecular cell research 5 32621840
2017 MPV17 hepatocerebral mitochondrial DNA depletion syndrome presenting as acute flaccid paralysis - A case report. Mitochondrion 5 28673863
2013 Novel c.191C>G (p.Pro64Arg) MPV17 mutation identified in two pairs of unrelated Polish siblings with mitochondrial hepatoencephalopathy. Clinical genetics 5 23829229
2013 Erratum: transparent, a gene affecting stripe formation in Zebrafish, encodes the mitochondrial protein Mpv17 that is required for iridophore survival. Biology open 5 24143285
2023 MPV17 mutation-related mitochondrial DNA depletion syndrome: A case series in infants. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology 4 36753038
2022 Outcomes after liver transplantation in MPV17 deficiency (Navajo neurohepatopathy): A single-center case series. Pediatric transplantation 4 35466509
2019 Esophageal 3D organoids of MPV17 mouse model of mitochondrial DNA depletion show epithelial cell plasticity and telomere attrition. Oncotarget 4 31692873
2021 MPV17 Gene Variant Mutation Presenting as Leucoencephalopathy with Peripheral Neuropathy. Neurology India 3 34979697
2020 MPV17 does not control cancer cell proliferation. PloS one 3 32155188
2016 A monoclonal antibody raised against bacterially expressed MPV17 sequences shows peroxisomal, endosomal and lysosomal localisation in U2OS cells. BMC research notes 3 26921094
2010 Functional splicing assay supporting that c.70 + 5G > A mutation in the MPV17 gene is disease causing. Journal of inherited metabolic disease 3 20614188
2022 A Drosophila model of the neurological symptoms in Mpv17-related diseases. Scientific reports 2 36587049
2016 MPV17-related hepatocerebral mitochondrial DNA depletion syndrome (MPV17-NNH) revisited. eNeurologicalSci 2 29473055
2014 A novel MPV17 gene mutation in a Saudi infant causing fatal progressive liver failure. Annals of Saudi medicine 2 24894789
2025 Mutation of mpv17 results in loss of iridophores due to mitochondrial dysfunction in tilapia. The Journal of heredity 1 38946032
2024 [MPV17 inhibits iron overload-induced ferroptosis of splenic CD3+ T cells in mice by blocking ERK pathway]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 38790095
2024 Liver transplantation for mitochondrial DNA depletion syndrome caused by MPV17 deficiency: a case report and literature review. Frontiers in surgery 1 39055132
2024 Establishment of a human induced pluripotent stem cell (iPSC) line (JUCTCi018-A) from a patient with Charcot-Marie-Tooth disease type 2EE (CMT2EE) due to a homozygous c.122G > A p.(Arg41Gln) mutation in the MPV17 gene. Stem cell research 1 39461114
2022 Comprehensive Analysis on the Specific Role and Function of Mitochondrial Inner Membrane Protein MPV17 in Liver Hepatocellular Carcinoma. Genetics research 1 35919033
2021 MPV17-related Hepatocerebral Mitochondrial DNA Depletion Syndrome. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 1 34035203
2026 Neonatal HIV prophylaxis is associated with accelerated presentation and clinical progression of MPV17-related mitochondrial neurohepatopathy. BMC pediatrics 0 42192320
2025 Retrospective observational study of the magnetic resonance imaging features of MPV17-related mitochondrial DNA depletion syndrome. Pediatric radiology 0 40773069
2024 Overexpression of MPV17/PMP22-like protein 2 gene decreases production of radical oxygen species in Pyropia yezoensis (Bangiales, Rhodophyta). Journal of phycology 0 38924097
2022 [Genetic testing and prenatal diagnosis for a Chinese pedigree affected with mitochondrial DNA depletion syndrome due to variant of MPV17 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 36184088
2015 Canine MPV17 truncation without clinical manifestations. Biology open 0 26353863

Missed literature

Know a paper Affinage missed for MPV17? Flag it for the maintainers and the community.

No submissions yet.