Cited by 107Mitochondrial Function and PathologyAutophagy in Disease and TherapyATP Synthase and ATPases Research

Inhibition of mitochondrial fission favours mutant over wild-type mitochondrial DNA

Malena, Adriana, Loro, Emanuele, Di Re, Miriam, Holt, Ian J., Vergani, Lodovica·2009·Human Molecular Genetics

Abstract

Biased segregation of mitochondrial DNA variants has been widely documented, but little was known about its molecular basis. We set out to test the hypothesis that altering the balance between mitochondrial fusion and fission could influence the segregation of mutant and wild-type mtDNA variants, because it would modify the number of organelles per cell. Therefore human cells heteroplasmic for the pathological A3243G mitochondrial DNA mutation were transfected with constructs designed to silence Drp1 or hFis1, whose gene products are required for mitochondrial fission. Drp1 and hFis1 gene silencing were both associated with increased levels of mutant mitochondrial DNA. Thus, the extent of the mitochondrial reticular network appears to be an important factor in determining mutant load. The fact that the level of mutant and wild-type mitochondrial DNA can be manipulated by altering the expression of nuclear encoded factors involved in mitochondrial fission suggests new interventions for mitochondrial DNA disorders.

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Crossref · 10.1093/hmg/ddp281

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  • Silencing of Drp1 and Fis1 genes in a human cell line heteroplasmic for a pathological mtDNA mutation increases the levels of mutant mtDNA compared with wild-type mtDNA.

    “Silencing of Drp1 and Fis1 genes in a human cell line heteroplasmic for a pathological mtDNA mutation increased the levels of mutant mtDNA compared with wild-type mtDNA (Malena et al., 2009).”

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Authors
Malena, A., Loro, E., Di Re, M., Holt, I. J., & Vergani, L.
Affiliations
  • University of Padua (IT)
  • MRC Mitochondrial Biology Unit (GB)
Corresponding author
  • Holt, Ian J.
  • Vergani, Lodovica
Venue
Human Molecular Genetics
Published
2009-06-27
Volume
18
Issue
18
Pages
3407-3416
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2131594084
Cited by
107
References
60
Citations by year
2026: 2 · 2025: 3 · 2024: 12 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 4 · 2013: 9 · 2012: 9
FWCI
3.47
Type
journal article
Language
en
Open access
closed
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
mitochondrial fission, mitochondrial fusion, mitochondrial DNA segregation, heteroplasmy, A3243G mutation, Drp1, gene silencing, mitochondrial DNA disorders
MeSH terms
Base Sequence, DNA, Mitochondrial, Humans, Membrane Proteins, Mitochondria, Molecular Sequence Data, Mutation, Down-Regulation, Gene Dosage, GTP Phosphohydrolases, Mitochondrial Proteins, Cell Line, Tumor

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