Transcomplementation between Different Types of Respiration-deficient Mitochondria with Different Pathogenic Mutant Mitochondrial DNAs

Takai, Daiya; Isobe, Kotoyo; Hayashi, Jun‐Ichi

doi:10.1074/jbc.274.16.11199

Cited by 37 publications

(36 citation statements)

References 22 publications

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“…The transcomplementing clones became established very sluggishly and exhibited in general slow growth and a substantial rate of cell death. The present results confirm the previous observations of transcomplementation of mtDNA mutations in human cell cultures (24,25). However, they are in striking contrast to the general model that has been proposed of human mitochondria functioning as a single dynamic unit in a living cell, with rapid diffusion of mtDNA and/or its products throughout the organelles (23).…”

Section: Discussioncontrasting

confidence: 42%

“…Other investigators, analyzing by fluorescence microscopy the fusion products of enucleated wild-type human cells and human 0 cells, obtained results that were interpreted to indicate the occurrence of a rapid and extensive fusion of host and exogenous mitochondria and subsequent rapid diffusion of mtDNA and its transcripts throughout the organelles (23). More recently, the same investigators (24,25), after constructing cybrids carrying two types of mtDNA with appropriate markers within distinct organelles and culturing them under conditions either selective or non-selective for recovery of respiratory capacity, isolated a few clones that showed evidence of translational complementation.…”

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confidence: 99%

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Very Rare Complementation between Mitochondria Carrying Different Mitochondrial DNA Mutations Points to Intrinsic Genetic Autonomy of the Organelles in Cultured Human Cells

Enríquez

Cabezas‐Herrera

Bayona‐Bafaluy

et al. 2000

Journal of Biological Chemistry

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In the present work, a large scale investigation was done regarding the capacity of cultured human cell lines (carrying in homoplasmic form either the mitochondrial tRNA Lys A8344G mutation associated with the myoclonic epilepsy and ragged red fiber (MERRF) encephalomyopathy or a frameshift mutation, isolated in vitro, in the gene for the ND4 subunit of NADH dehydrogenase) to undergo transcomplementation of their recessive mitochondrial DNA (mtDNA) mutations after cell fusion. The presence of appropriate nuclear drug resistance markers in the two cell lines allowed measurements of the frequency of cell fusion in glucose-containing medium, non-selective for respiratory capacity, whereas the frequency of transcomplementation of the two mtDNA mutations was determined by growing the same cell fusion mixture in galactose-containing medium, selective for respiratory competence. Transcomplementation of the two mutations was revealed by the re-establishment of normal mitochondrial protein synthesis and respiratory activity and by the relative rates synthesis of two isoforms of the ND3 subunit of NADH dehydrogenase. The results of several experiments showed a cell fusion frequency between 1.4 and 3.4% and an absolute transcomplementation frequency that varied between 1.2 ؋ 10 ؊5 and 5.5 ؋ 10 ؊4 . Thus, only 0.3-1.6% of the fusion products exhibited transcomplementation of the two mutations. These rare transcomplementing clones were very sluggish in developing, grew very slowly thereafter, and showed a substantial rate of cell death (22-28%). The present results strongly support the conclusion that the capacity of mitochondria to fuse and mix their contents is not a general intrinsic property of these organelles in mammalian cells, although it may become activated in some developmental or physiological situations.

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Section: Discussioncontrasting

confidence: 42%

mentioning

confidence: 99%

Very Rare Complementation between Mitochondria Carrying Different Mitochondrial DNA Mutations Points to Intrinsic Genetic Autonomy of the Organelles in Cultured Human Cells

Enríquez

Cabezas‐Herrera

Bayona‐Bafaluy

et al. 2000

Journal of Biological Chemistry

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“…The fact that mitochondrial fusions do occur revives an earlier idea that the selection advantage of deletion mutants is their reduced size, which allows them to replicate faster than WT (22)(23)(24). This idea had fallen into disfavor because even though the mutant might have a replication advantage it should also suffer from a severe lack of ATP and a reduced proton gradient, both of which are important for fast mitochondrial growth.…”

Section: Accumulation Of Mitochondrial Mutantsmentioning

confidence: 93%

Evolution of the mitochondrial fusion–fission cycle and its role in aging

Kowald

Kirkwood

2011

Proc. Natl. Acad. Sci. U.S.A.

115

109

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Mitochondria are organelles of eukaryotic cells that contain their own genetic material and evolved from prokaryotic ancestors some 2 billion years ago. They are the main source of the cell's energy supply and are involved in such important processes as apoptosis, mitochondrial diseases, and aging. During recent years it also became apparent that mitochondria display a complex dynamical behavior of fission and fusion, the function of which is as yet unknown. In this paper we develop a concise theory that explains why fusion and fission have evolved, how these processes are related to the accumulation of mitochondrial mutants during aging, why the mitochondrial DNA has to be located close to the respiration complexes where most radicals are generated, and what selection pressures shaped the slightly different structure of animal and plant mitochondria. We believe that this “organelle control” theory will help in understanding key processes involved in the evolution of the mitochondrial genome and the aging process.

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“…As we have remarked earlier, there is no evidence that DNA can be taken up by mitochondria, and the evidence for mitochondrial fusion is contradictory. Experiments with human cell lines seeded with different types of mutant mitochondria suggest that mitochondrial fusion is very rare, in cell lines at least, since there is little, if any, complementation (Enriquez et al 2000;Takai et al 1999). However, fusion does appear to occur at some stages of development, including embryogenesis (Smith and Alcivar 1993).…”

Section: Paternal Leakagementioning

confidence: 99%

Does Human mtDNA Recombine?

Eyre‐Walker

Awadalla

2001

Journal of Molecular Evolution

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Abstract. In this article we review the evidence for and against recombination in human mtDNA. If recombination occurs, there needs to be a route by which genetic material can incorporate itself into the mitochondrial genome, and hence between mitochondrial lineages. We review the evidence for possible routes and then review the current state of the population genetic evidence for recombination. We conclude that there is no firmly established route by which recombination can occur, and that while some of the population genetic evidence is suggestive of recombination, it is far from conclusive.

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Transcomplementation between Different Types of Respiration-deficient Mitochondria with Different Pathogenic Mutant Mitochondrial DNAs

Cited by 37 publications

References 22 publications

Very Rare Complementation between Mitochondria Carrying Different Mitochondrial DNA Mutations Points to Intrinsic Genetic Autonomy of the Organelles in Cultured Human Cells

Very Rare Complementation between Mitochondria Carrying Different Mitochondrial DNA Mutations Points to Intrinsic Genetic Autonomy of the Organelles in Cultured Human Cells

Evolution of the mitochondrial fusion–fission cycle and its role in aging

Does Human mtDNA Recombine?

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