Origin, transmission, and segregation of mitochondrial DNA dimers in mouse hybrid and cybrid cell lines

1984 ◽  
Vol 10 (3) ◽  
pp. 259-274 ◽  
Author(s):  
Neil Howell ◽  
P. Huang ◽  
Richard D. Kolodner
Keyword(s):  
Mitochondrial Dna ◽  
Cell Lines ◽  
Cybrid Cell

Mitochondrial DNA–Related Mitochondrial Dysfunction in Neurodegenerative Diseases

2002 ◽  
Vol 126 (3) ◽  
pp. 271-280
Author(s):  
Russell H. Swerdlow
Keyword(s):  
Cell Death ◽  
Mitochondrial Dna ◽  
Programmed Cell Death ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Cell Lines ◽  
Late Onset ◽  
Cell Death Pathways ◽  
Mitochondrial Genotype ◽  
Cybrid Cell

Abstract Mitochondrial dysfunction occurs in several late-onset neurodegenerative diseases. Determining its origin and significance may provide insight into the pathogeneses of these disorders. Regarding origin, one hypothesis proposes mitochondrial dysfunction is driven by mitochondrial DNA (mtDNA) aberration. This hypothesis is primarily supported by data from studies of cytoplasmic hybrid (cybrid) cell lines, which facilitate the study of mitochondrial genotype-phenotype relationships. In cybrid cell lines in which mtDNA from persons with certain neurodegenerative diseases is assessed, mitochondrial physiology is altered in ways that are potentially relevant to programmed cell death pathways. Connecting mtDNA-related mitochondrial dysfunction with programmed cell death underscores the crucial if not central role for these organelles in neurodegenerative pathophysiology. This review discusses the cybrid technique and summarizes cybrid data implicating mtDNA-related mitochondrial dysfunction in certain neurodegenerative diseases.

scholarly journals Gene expression of cytokines and cytokine receptors is modulated by the common variability of the mitochondrial DNA in cybrid cell lines

2006 ◽  
Vol 11 (8) ◽  
pp. 883-891 ◽  
Author(s):  
Dina Bellizzi ◽  
Paola Cavalcante ◽  
Daniela Taverna ◽  
Giuseppina Rose ◽  
Giuseppe Passarino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Cell Lines ◽  
Cytokine Receptors ◽  
The Common ◽  
Cybrid Cell

scholarly journals Mitochondrial DNA Manipulations Affect Tau Oligomerization

2020 ◽  
Vol 77 (1) ◽  
pp. 149-163
Author(s):  
Ian W. Weidling ◽  
Heather M. Wilkins ◽  
Scott J. Koppel ◽  
Lewis Hutfles ◽  
Xiaowan Wang ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Cytochrome Oxidase ◽  
Cell Lines ◽  
Oxidase Activity ◽  
Mtdna Depletion ◽  
Mitochondrial Transfer ◽  
Mitochondrial Toxins ◽  
Tau Aggregation ◽  
Cybrid Cell

Background: Mitochondrial dysfunction and tau aggregation occur in Alzheimer’s disease (AD), and exposing cells or rodents to mitochondrial toxins alters their tau. Objective: To further explore how mitochondria influence tau, we measured tau oligomer levels in human neuronal SH-SY5Y cells with different mitochondrial DNA (mtDNA) manipulations. Methods: Specifically, we analyzed cells undergoing ethidium bromide-induced acute mtDNA depletion, ρ0 cells with chronic mtDNA depletion, and cytoplasmic hybrid (cybrid) cell lines containing mtDNA from AD subjects. Results: We found cytochrome oxidase activity was particularly sensitive to acute mtDNA depletion, evidence of metabolic re-programming in the ρ0 cells, and a relatively reduced mtDNA content in cybrids generated through AD subject mitochondrial transfer. In each case tau oligomer levels increased, and acutely depleted and AD cybrid cells also showed a monomer to oligomer shift. Conclusion: We conclude a cell’s mtDNA affects tau oligomerization. Overlapping tau changes across three mtDNA-manipulated models establishes the reproducibility of the phenomenon, and its presence in AD cybrids supports its AD-relevance.

Depletion of mitochondrial DNA by ddC in untransformed human cell lines

1997 ◽  
Vol 23 (4) ◽  
pp. 287-290 ◽  
Author(s):  
Isabelle Nelson ◽  
Michael G. Hanna ◽  
Nicholas W. Wood ◽  
A. E. Harding
Keyword(s):  
Mitochondrial Dna ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Lines

scholarly journals Investigations of the mechanism by which mammalian cell growth is inhibited by N1N12-bis(ethyl)spermine

1993 ◽  
Vol 291 (1) ◽  
pp. 131-137 ◽  
Author(s):  
L Albanese ◽  
R J Bergeron ◽  
A E Pegg
Keyword(s):  
Mitochondrial Dna ◽  
Cell Growth ◽  
Cell Lines ◽  
Ornithine Decarboxylase ◽  
Polyamine Analogues ◽  
Proliferative Effect ◽  
L1210 Cells ◽  
Inhibition Of Growth ◽  
Variant Cell ◽  
Mammalian Cell Growth

N1N12-Bis(ethyl)spermine (BESM) and related compounds are powerful inhibitors of cell growth that may have potential as anti-neoplastic agents [Bergeron, Neims, McManis, Hawthorne, Vinson, Bortell and Ingeno (1988) J. Med. Chem. 31, 1183-1190]. The mechanism by which these compounds bring about their effects was investigated by using variant cell lines in which processes thought to be altered by these agents are perturbed. Comparisons between the response of these cells and of their parental equivalents to BESM, N1N11-bis(ethyl)norspermine, N1N14-bis(ethyl)homospermine and N1N8-bis(ethyl)spermidine were then made. It was found that D-R cells, an L1210-derived line that over-expresses ornithine decarboxylase, were not resistant to these compounds. This indicates that the decrease in ornithine decarboxylase is not critical for the action of the compounds on cell growth. Furthermore, although polyamine levels were decreased in the D-R cells, the content was not totally depleted, indicating that such depletion is also not essential for the anti-proliferative effect. Two cell lines lacking mitochondrial DNA (human 143B206 cells and chicken DU3 cells) did not differ in sensitivity to BESM from their parental 143BTK- and DU24 cells. Furthermore, the inhibition of respiration in L1210 cells in response to BESM developed more slowly than the inhibition of growth. Thus it appears that the inhibitions of mitochondrial DNA synthesis and of mitochondrial respiration are also not primary factors in the anti-proliferative effects of these polyamine analogues. The inhibition of growth did, however, correlate with the intracellular accumulation of the analogues. It appears that the bis(ethyl)polyamine derivatives act by binding to intracellular target molecules and preventing macromolecular synthesis. The decline in normal polyamines may facilitate such binding, but is not essential for growth arrest.

scholarly journals Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation

2008 ◽  
Vol 181 (7) ◽  
pp. 1117-1128 ◽  
Author(s):  
Robert W. Gilkerson ◽  
Eric A. Schon ◽  
Evelyn Hernandez ◽  
Mercy M. Davidson
Keyword(s):  
Mitochondrial Dna ◽  
Protein Synthesis ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Mitochondrial Protein ◽  
Functional Complementation ◽  
Mitochondrial Protein Synthesis ◽  
Protein Assemblies ◽  
Mtdna Mutations ◽  
Mitochondrial Nucleoids

Mitochondrial DNA (mtDNA) is packaged into DNA-protein assemblies called nucleoids, but the mode of mtDNA propagation via the nucleoid remains controversial. Two mechanisms have been proposed: nucleoids may consistently maintain their mtDNA content faithfully, or nucleoids may exchange mtDNAs dynamically. To test these models directly, two cell lines were fused, each homoplasmic for a partially deleted mtDNA in which the deletions were nonoverlapping and each deficient in mitochondrial protein synthesis, thus allowing the first unequivocal visualization of two mtDNAs at the nucleoid level. The two mtDNAs transcomplemented to restore mitochondrial protein synthesis but were consistently maintained in discrete nucleoids that did not intermix stably. These results indicate that mitochondrial nucleoids tightly regulate their genetic content rather than freely exchanging mtDNAs. This genetic autonomy provides a molecular mechanism to explain patterns of mitochondrial genetic inheritance, in addition to facilitating therapeutic methods to eliminate deleterious mtDNA mutations.

SV40-transformed hamster cells resistant to 100–250 microgram/ml of ethidium bromide

1978 ◽  
Vol 33 (1) ◽  
pp. 157-169
Author(s):  
G. Wolf ◽  
L. Tejmar ◽  
S. Borell ◽  
W. Klietman
Keyword(s):  
Mitochondrial Dna ◽  
Cell Lines ◽  
Ethidium Bromide ◽  
Gel Electrophoresis ◽  
Mitochondrial Proteins ◽  
Wild Type ◽  
Mitochondrial Ultrastructure ◽  
Gold Hamsters ◽  
Resistant Cells

SV40-transformed hamster cells were selected for resistance to ethidium bromide (EB). Several cell lines were established, which grew in the presence of up to 250 microgram/ml EB. The EB resistance is genetically stable. The cloned resistant cells show no difference in morphology, with the exception of the mitochondrial ultrastructure, which exhibits condensed cristae formation. The tumorigenicity of these cells in Syrian gold hamsters is considerably reduced. Incorporation of radioactive labelled thymidine into mitochondrial DNA is not influenced by the presence of the drug. Gel electrophoresis with mitochondrial proteins from wild-type and resistant cells reveals significantly different patterns. The mechanism of EB resistance is discussed.

scholarly journals Creation of Cybrid Cultures Containing mtDNA Mutations m.12315G>A and m.1555G>A, Associated with Atherosclerosis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 499 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Vasily V. Sinyov ◽  
Anastasia I. Ryzhkova ◽  
Marina D. Sazonova ◽  
Zukhra B. Khasanova ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Drug Therapy ◽  
Mitochondrial Genome ◽  
Cell Lines ◽  
Threshold Value ◽  
Mtdna Mutation ◽  
Single Nucleotide ◽  
Mtdna Mutations ◽  
Cybrid Cell ◽  
In Cells

In the present work, a pilot creation of four cybrid cultures with high heteroplasmy level was performed using mitochondrial genome mutations m.12315G>A and m.1555G>A. According to data of our preliminary studies, the threshold heteroplasmy level of mutation m.12315G>A is associated with atherosclerosis. At the same time, for a mutation m.1555G>A, such a heteroplasmy level is associated with the absence of atherosclerosis. Cybrid cultures were created by fusion of rho0-cells and mitochondria from platelets with a high heteroplasmy level of the investigated mutations. To create rho0-cells, THP-1 culture of monocytic origin was taken. According to the results of the study, two cybrid cell lines containing mutation m.12315G>A with the heteroplasmy level above the threshold value (25% and 44%, respectively) were obtained. In addition, two cybrid cell lines containing mutation m.1555G>A with a high heteroplasmy level (24%) were obtained. Cybrid cultures with mtDNA mutation m.12315G>A can be used to model both the occurrence and development of atherosclerosis in cells and the titration of drug therapy for patients with atherosclerosis. With the help of cybrid cultures containing single nucleotide replacement of mitochondrial genome m.1555G>A, it is possible to develop approaches to the gene therapy of atherosclerosis.

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