Cited by 420Mitochondrial Function and PathologyAutophagy in Disease and TherapyDNA Repair Mechanisms

Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria

Ono, Tomoko, Isobe, Kotoyo, Nakada, Kazuto, Hayashi, Jun-Ichi·2001·Nature Genetics

Abstract

Extensive complementation between fused mitochondria is indicated by recombination of 'parental' mitochondrial (mt) DNA (ref. 1,2) of yeast and plant cells. It has been difficult, however, to demonstrate the occurrence of complementation between fused mitochondria in mammalian species through the presence of recombinant mtDNA molecules, because sequence of mtDNA throughout an individual tends to be uniform owing to its strictly maternal inheritance. We isolated two types of respiration-deficient cell lines, with pathogenic mutations in mitochondrial tRNAIle or tRNALeu(UUR) genes from patients with mitochondrial diseases. The coexistence of their mitochondria within hybrids restored their normal morphology and respiratory enzyme activity by 10-14 days after fusion, indicating the presence of an extensive and continuous exchange of genetic contents between the mitochondria. This complementation between fused mitochondria may represent a defence of highly oxidative organelles against mitochondrial dysfunction caused by the accumulation of mtDNA lesions with age.

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Crossref · 10.1038/90116

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Authors
Ono, T., Isobe, K., Nakada, K., & Hayashi, J.-I.
Affiliations
University of Tsukuba (JP)
Corresponding author
Hayashi, Jun-Ichi
Venue
Nature Genetics
Published
2001-07
Volume
28
Issue
3
Pages
272-275
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W1554250492
Cited by
420
References
29
Citations by year
2026: 7 · 2025: 14 · 2024: 14 · 2023: 10 · 2022: 16 · 2021: 24 · 2020: 18 · 2019: 15 · 2018: 10 · 2017: 24 · 2016: 13 · 2015: 21 · 2014: 21 · 2013: 11 · 2012: 28
FWCI
5.94
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
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 › DNA Repair Mechanisms
Keywords
mitochondrial fusion, mitochondrial recombination, mitochondrial dysfunction, mitochondrial tRNA mutations, mitochondrial disease, respiratory deficiency, oxidative stress, human cell lines
MeSH terms
DNA, Mitochondrial, Genetic Complementation Test, Humans, Hybrid Cells, Intracellular Membranes, Membrane Fusion, Mitochondria, Oxygen Consumption, RNA, Transfer, Ile, RNA, Transfer, Leu, Mitochondrial Myopathies

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