Evidence map›Paper›PMID 25501370›Full record

ArticleMolecular biology of the cell2015

Genetic mosaic analysis of a deleterious mitochondrial DNA mutation in Drosophila reveals novel aspects of mitochondrial regulation and function.

Zhe Chen, Yun Qi, Stephanie French, Guofeng Zhang, Raúl Covian Garcia, Robert Balaban, Hong Xu

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 63 citations in OpenAlex.

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  12. Insights fromFrontiers in neuroscience · 2023
    Review
  13. Article
  14. Mitigation of age-dependent accumulation of defective mitochondrial genomes.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  15. Article
  16. Article
  17. Mitochondrial function in development and disease.Disease models & mechanisms · 2021
    Review
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Zhe ChenLaboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20892.
Yun QiLaboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20892.
Stephanie FrenchLaboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Guofeng ZhangNational Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
Raúl Covian GarciaLaboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Robert BalabanLaboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Hong XuLaboratory of Molecular Genetics, National Institutes of Health, Bethesda, MD 20892 hong.xu@nih.gov.
National Institutes of Health · USNational Heart Lung and Blood Institute · US

Funding

Mitochondrial DNA inheritance in DrosophilaZIAHL006153 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI XU, HONG · 2012 to 2025
$26.5M
Control Of Cellular Energy MetabolismZIAHL004601 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BALABAN, ROBERT · 2009 to 2023
$24.4M
Electron MicroscopyZICEB000080 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI ZHANG, GUOFENG · 2011 to 2025
$8.2M
Intramural NIH HHS
6 · The paper itself

Abstract

Various human diseases are associated with mitochondrial DNA (mtDNA) mutations, but heteroplasmy—the coexistence of mutant and wild-type mtDNA—complicates their study. We previously isolated a temperature-lethal mtDNA mutation in Drosophila, mt:CoI(T300I), which affects the cytochrome c oxidase subunit I (CoI) locus. In the present study, we found that the decrease in cytochrome c oxidase (COX) activity was ascribable to a temperature-dependent destabilization of cytochrome a heme. Consistently, the viability of homoplasmic flies at 29°C was fully restored by expressing an alternative oxidase, which specifically bypasses the cytochrome chains. Heteroplasmic flies are fully viable and were used to explore the age-related and tissue-specific phenotypes of mt:CoI(T300I). The proportion of mt:CoI(T300I) genome remained constant in somatic tissues along the aging process, suggesting a lack of quality control mechanism to remove defective mitochondria containing a deleterious mtDNA mutation. Using a genetic scheme that expresses a mitochondrially targeted restriction enzyme to induce tissue-specific homoplasmy in heteroplasmic flies, we found that mt:CoI(T300I) homoplasmy in the eye caused severe neurodegeneration at 29°C. Degeneration was suppressed by improving mitochondrial Ca(2+) uptake, suggesting that Ca(2+) mishandling contributed to mt:CoI(T300I) pathogenesis. Our results demonstrate a novel approach for Drosophila mtDNA genetics and its application in modeling mtDNA diseases.

Indexed as

AnimalsCalcium SignalingCompound Eye, ArthropodDNA, MitochondrialDNA Mutational AnalysisDrosophilaDrosophila ProteinsElectron Transport Complex IVGenome, MitochondrialMitochondriaModels, GeneticDNA, MitochondrialDrosophila ProteinsElectron Transport Complex IV

Identifiers

PMID25501370
PMCPMC4325838
OpenAlexW2136320301

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.