scholarly journals In vivo control of respiration by cytochrome c oxidase in wild-type and mitochondrial DNA mutation-carrying human cells

1997 ◽  
Vol 94 (4) ◽  
pp. 1166-1171 ◽  
Author(s):  
G. Villani ◽  
G. Attardi
Keyword(s):  
Mitochondrial Dna ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Human Cells ◽  
Control Of Respiration ◽  
Wild Type ◽  
Mitochondrial Dna Mutation ◽  
Dna Mutation

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

2015 ◽  
Vol 26 (4) ◽  
pp. 674-684 ◽  
Author(s):  
Zhe Chen ◽  
Yun Qi ◽  
Stephanie French ◽  
Guofeng Zhang ◽  
Raúl Covian Garcia ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mtdna Mutation ◽  
Mitochondrial Dna Mutation ◽  
Tissue Specific ◽  
Dna Mutation ◽  
Mtdna Mutations ◽  
Genetic Mosaic ◽  
Age Related

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:CoIT300I, 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:CoIT300I. The proportion of mt:CoIT300I 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:CoIT300I homoplasmy in the eye caused severe neurodegeneration at 29°C. Degeneration was suppressed by improving mitochondrial Ca2+ uptake, suggesting that Ca2+ mishandling contributed to mt:CoIT300I pathogenesis. Our results demonstrate a novel approach for Drosophila mtDNA genetics and its application in modeling mtDNA diseases.

Mitochondrial DNA Mutation and Depletion Increase the Susceptibility of Human Cells to Apoptosis

2004 ◽  
Vol 1011 (1) ◽  
pp. 133-145 ◽  
Author(s):  
CHUN-YI LIU ◽  
CHENG-FENG LEE ◽  
CHIUNG-HUI HONG ◽  
YAU-HUEI WEI
Keyword(s):  
Mitochondrial Dna ◽  
Human Cells ◽  
Mitochondrial Dna Mutation ◽  
Dna Mutation

scholarly journals Induction and characterization of mitochondrial DNA mutants in Chlamydomonas reinhardtii.

1989 ◽  
Vol 108 (4) ◽  
pp. 1221-1226 ◽  
Author(s):  
R F Matagne ◽  
M R Michel-Wolwertz ◽  
C Munaut ◽  
C Duyckaerts ◽  
F Sluse
Keyword(s):  
Mitochondrial Dna ◽  
Cytochrome C ◽  
Chlamydomonas Reinhardtii ◽  
Cytochrome C Oxidase ◽  
Oxidase Activity ◽  
Wild Type ◽  
Apocytochrome B ◽  
Cytochrome Pathway ◽  
Apocytochrome B Gene

In addition to lethal minute colony mutations which correspond to loss of mitochondrial DNA, acriflavin induces in Chlamydomonas reinhardtii a low percentage of cells that grow in the light but do not divide under heterotrophic conditions. Two such obligate photoautotrophic mutants were shown to lack the cyanide-sensitive cytochrome pathway of the respiration and to have a reduced cytochrome c oxidase activity. In crosses to wild type, the mutations are transmitted almost exclusively from the mating type minus parent. A same pattern of inheritance is seen for the mitochondrial DNA in crosses between the two interfertile species C. reinhardtii and Chlamydomonas smithii. Both mutants have a deletion in the region of the mitochondrial DNA containing the apocytochrome b gene and possibly the unidentified URFx gene.

scholarly journals Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles

1994 ◽  
Vol 14 (4) ◽  
pp. 2699-2712
Author(s):  
M Yoneda ◽  
T Miyatake ◽  
G Attardi
Keyword(s):  
Mitochondrial Dna ◽  
Mammalian Cells ◽  
Wild Type ◽  
Mitochondrial Dna Mutation ◽  
Experimental Conditions ◽  
Chloramphenicol Resistance ◽  
Dna Mutation ◽  
Mitochondrial Dnas ◽  
A Cell ◽  
Type Gene

The rules that govern complementation of mutant and wild-type mitochondrial genomes in human cells were investigated under different experimental conditions. Among mitochondrial transformants derived from an individual affected by the MERRF (myoclonus epilepsy associated with ragged red fibers) encephalomyopathy and carrying in heteroplasmic form the mitochondrial tRNA(Lys) mutation associated with that syndrome, normal protein synthesis and respiration was observed when the wild-type mitochondrial DNA exceeded 10% of the total complement. In these transformants, the protective effect of wild-type mitochondrial DNA was shown to involve interactions of the mutant and wild-type gene products. Very different results were obtained in experiments in which two mitochondrial DNAs carrying nonallelic disease-causing mutations were sequentially introduced within distinct organelles into the same human mitochondrial DNA-less (rho 0) cell. In transformants exhibiting different ratios of the two genomes, no evidence of cooperation between their products was observed, even 3 months after the introduction of the second mutation. These results pointed to the phenotypic independence of the two genomes. A similar conclusion was reached in experiments in which mitochondria carrying a chloramphenicol resistance-inducing mitochondrial DNA mutation were introduced into chloramphenicol-sensitive cells. A plausible interpretation of the different results obtained in the latter two sets of experiments, compared with the complementation behavior observed in the heteroplasmic MERRF transformants, is that in the latter, the mutant and wild-type genomes coexisted in the same organelles from the time of the mutation. This would imply that the way in which mitochondrial DNA is sorted among different organelles plays a fundamental role in determining the oxidative-phosphorylation phenotype in mammalian cells. These results have significant implications for mitochondrial genetics and for studies on the transmission and therapy of mitochondrial DNA-linked diseases.

Decreased heat shock protein 27 expression and altered autophagy in human cells harboring A8344G mitochondrial DNA mutation

Mitochondrion ◽  
2011 ◽  
Vol 11 (5) ◽  
pp. 739-749 ◽  
Author(s):  
Chin-Yi Chen ◽  
Hsueh-Fu Chen ◽  
Siao-Jhen Gi ◽  
Tang-Hao Chi ◽  
Che-Kun Cheng ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 27 ◽  
Human Cells ◽  
Mitochondrial Dna Mutation ◽  
Dna Mutation

Effects of carbonic anhydrase-related protein VIII on human cells harbouring an A8344G mitochondrial DNA mutation

2014 ◽  
Vol 459 (1) ◽  
pp. 149-160 ◽  
Author(s):  
Tze-Kai Wang ◽  
Che-Kun Cheng ◽  
Tang-Hao Chi ◽  
Yi-Shing Ma ◽  
Shi-Bei Wu ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Carbonic Anhydrase ◽  
Human Cells ◽  
Related Protein ◽  
Mitochondrial Dna Mutation ◽  
Dna Mutation ◽  
Phosphorylated Akt

We show a significant decrease in CA8 in cybrids harbouring the MERRF A8344G mutation and overexpression of CA8 desensitizes mutant MERRF cybrids to apoptotic stress. Phosphorylated Akt is involved in the protection of cells by CA8 in MERRF cybrids.

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