ArticleHuman molecular genetics2015
POLG2 disease variants: analyses reveal a dominant negative heterodimer, altered mitochondrial localization and impaired respiratory capacity.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- Retrograde mitochondrial transport is required for mitochondrial biogenesis in zebrafish neurons.Nature communications · 2026Article
- Model organisms in POLG-related disorders: insights from yeast to multicellular systems.Cell death & disease · 2025Review
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Coordinated DNA polymerization by Polγ and the region of LonP1 regulated proteolysis.Nucleic acids research · 2024Article
- Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.Frontiers in oncology · 2024Review
- Structure-specific roles for PolG2-DNA complexes in maintenance and replication of mitochondrial DNA.Nucleic acids research · 2023Article
- Article
- Identification of Somatic Mitochondrial DNA Mutations, Heteroplasmy, and Increased Levels of Catenanes in Tumor Specimens Obtained from Three Endometrial Cancer Patients.Life (Basel, Switzerland) · 2022Article
- Mitochondrial protein dysfunction in pathogenesis of neurological diseases.Frontiers in molecular neuroscience · 2022Review
- VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum-mitochondria interactions.Molecular biology of the cell · 2021Article
- MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile.Frontiers in cellular neuroscience · 2021Article
- Visualizing, quantifying, and manipulating mitochondrial DNA in vivo.The Journal of biological chemistry · 2020Review
- Analysis of Mitochondrial DNA Polymorphisms in the Human Cell Lines HepaRG and SJCRH30.International journal of molecular sciences · 2019Article
- Analysis of Human Mitochondrial DNA Content by Southern Blotting and Nonradioactive Probe Hybridization.Current protocols in toxicology · 2019Article
- An N-Ethyl-N-Nitrosourea (ENU)-Induced Tyr265Stop Mutation of the DNA Polymerase Accessory Subunit Gamma 2 (Polg2) Is Associated With Renal Calcification in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Comparison of HepaRG cells following growth in proliferative and differentiated culture conditions reveals distinct bioenergetic profiles.Cell cycle (Georgetown, Tex.) · 2019Article
- POLG-related disorders and their neurological manifestations.Nature reviews. Neurology · 2019Review
- Characterization of the human homozygous R182W POLG2 mutation in mitochondrial DNA depletion syndrome.PloS one · 2018Article
- Inherited mitochondrial genomic instability and chemical exposures.Toxicology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Human mitochondrial DNA (mtDNA) is replicated and repaired by the mtDNA polymerase gamma, polγ. Polγ is composed of three subunits encoded by two nuclear genes: (1) POLG codes for the 140-kilodalton (kDa) catalytic subunit, p140 and (2) POLG2 encodes the ∼110-kDa homodimeric accessory subunit, p55. Specific mutations are associated with POLG- or POLG2-related disorders. During DNA replication the p55 accessory subunit binds to p140 and increases processivity by preventing polγ's dissociation from the template. To date, studies have demonstrated that homodimeric p55 disease variants are deficient in the ability to stimulate p140; however, all patients currently identified with POLG2-related disorders are heterozygotes. In these patients, we expect p55 to occur as 25% wild-type (WT) homodimers, 25% variant homodimers and 50% heterodimers. We report the development of a tandem affinity strategy to isolate p55 heterodimers. The WT/G451E p55 heterodimer impairs polγ function in vitro, demonstrating that the POLG2 c.1352G>A/p.G451E mutation encodes a dominant negative protein. To analyze the subcellular consequence of disease mutations in HEK293 cells, we designed plasmids encoding p55 disease variants tagged with green fluorescent protein (GFP). P205R and L475DfsX2 p55 variants exhibit irregular diffuse mitochondrial fluorescence and unlike WT p55, they fail to form distinct puncta associated with mtDNA nucleoids. Furthermore, homogenous preparations of P205R and L475DfsX2 p55 form aberrant reducible multimers. We predict that abnormal protein folding or aggregation or both contribute to the pathophysiology of these disorders. Examination of mitochondrial bioenergetics in stable cell lines overexpressing GFP-tagged p55 variants revealed impaired mitochondrial reserve capacity.
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.