scholarly journals Heteroplasmic mutations of the mitochondrial genome cause paradoxical effects on mitochondrial functions

2012 ◽  
Vol 26 (12) ◽  
pp. 4914-4924 ◽  
Author(s):  
Chengkang Zhang ◽  
Vincent H. Huang ◽  
Mariella Simon ◽  
Lokendra K. Sharma ◽  
Weiwei Fan ◽  
...  
2017 ◽  
Vol 34 (8) ◽  
pp. 1947-1959 ◽  
Author(s):  
Jean-Baptiste Leducq ◽  
Mathieu Henault ◽  
Guillaume Charron ◽  
Lou Nielly-Thibault ◽  
Yves Terrat ◽  
...  

Abstract Genome recombination is a major source of genotypic diversity and contributes to adaptation and speciation following interspecies hybridization. The contribution of recombination in these processes has been thought to be largely limited to the nuclear genome because organelles are mostly uniparentally inherited in animals and plants, which prevents recombination. Unicellular eukaryotes such as budding yeasts do, however, transmit mitochondria biparentally, suggesting that during hybridization, both parents could provide alleles that contribute to mitochondrial functions such as respiration and metabolism in hybrid populations or hybrid species. We examined the dynamics of mitochondrial genome transmission and evolution during speciation by hybridization in the natural budding yeast Saccharomyces paradoxus. Using population-scale mitochondrial genome sequencing in two endemic North American incipient species SpB and SpC and their hybrid species SpC*, we found that both parental species contributed to the hybrid mitochondrial genome through recombination. We support our findings by showing that mitochondrial recombination between parental types is frequent in experimental crosses that recreate the early step of this speciation event. In these artificial hybrids, we observed that mitochondrial genome recombination enhances phenotypic variation among diploid hybrids, suggesting that it could play a role in the phenotypic differentiation of hybrid species. Like the nuclear genome, the mitochondrial genome can, therefore, also play a role in hybrid speciation.


2019 ◽  
Vol 19 (3) ◽  
pp. 619-632
Author(s):  
Krzysztof Kowal ◽  
Brygida Ślaska ◽  
Adam Bownik ◽  
Beata Horecka ◽  
Jan Gawor ◽  
...  

AbstractThe aim of the study was to find associations between the process of neoplastic transformation and mtDNA mutations/polymorphisms, i.e. factors with potential prognostic significance, and to determine their impact on the biochemical properties, as well as structural, and functional properties of proteins. Blood and neoplastic tissue samples were collected from a 9-year-old Labrador dog with a diagnosed malignant mammary tumour. Next-generation genome sequencing (NGS) of the entire mitochondrial genome was performed using Illumina technology, and bioinformatics analyses were carried out. This is the first report demonstrating the application of NGS in the analysis of the canine mtDNA genome in neoplastic disease. The proposed strategy is innovative and promising. For the first time in the literature, the sequence of 29 genes was analysed to determine their association with the prevalence of tumour. In total, 32 polymorphic loci and 15 mutations were identified. For the first time, as many as 24 polymorphisms and all the mutations have been described to be associated with the neoplastic process in dogs. Most polymorphisms/mutations were found in the D-loop (31% of the polymorphisms and 93% of the mutations) and the COX1 gene sequence (16% of the polymorphisms). Blood or cancer heteroplasmy was noted in 93% of the mutations. Four of the 18 polymorphisms detected in the protein-coding genes were non-synonymous polymorphisms that have not been described in the literature so far (m.T7593C in COX2, m.G8807A in COX3, m.A9911G in ND4L, and m.T13299A in ND5) but resulted in changes in amino acids in proteins. These mutations and polymorphisms can affect mitochondrial functions and may be a result of cell adaptation to the changes in the environment occurring during carcinogenesis. The replacement of “wild type” mtDNA by a mutated molecule may be an important phenomenon accompanying carcinogenesis.


2017 ◽  
Vol 131 (9) ◽  
pp. 865-881 ◽  
Author(s):  
Jan Neckář ◽  
Anna Svatoňová ◽  
Romana Weissová ◽  
Zdeněk Drahota ◽  
Pavlína Zajíčková ◽  
...  

Mitochondria play an essential role in improved cardiac ischaemic tolerance conferred by adaptation to chronic hypoxia. In the present study, we analysed the effects of continuous normobaric hypoxia (CNH) on mitochondrial functions, including the sensitivity of the mitochondrial permeability transition pore (MPTP) to opening, and infarct size (IS) in hearts of spontaneously hypertensive rats (SHR) and the conplastic SHR-mtBN strain, characterized by the selective replacement of the mitochondrial genome of SHR with that of the more ischaemia-resistant brown Norway (BN) strain. Rats were adapted to CNH (10% O2, 3 weeks) or kept at room air as normoxic controls. In the left ventricular mitochondria, respiration and cytochrome c oxidase (COX) activity were measured using an Oxygraph-2k and the sensitivity of MPTP opening was assessed spectrophotometrically as Ca2+-induced swelling. Myocardial infarction was analysed in anaesthetized open-chest rats subjected to 20 min of coronary artery occlusion and 3 h of reperfusion. The IS reached 68±3.0% and 65±5% of the area at risk in normoxic SHR and SHR-mtBN strains, respectively. CNH significantly decreased myocardial infarction to 46±3% in SHR. In hypoxic SHR-mtBN strain, IS reached 33±2% and was significantly smaller compared with hypoxic SHR. Mitochondria isolated from hypoxic hearts of both strains had increased detergent-stimulated COX activity and were less sensitive to MPTP opening. The maximum swelling rate was significantly lower in hypoxic SHR-mtBN strain compared with hypoxic SHR, and positively correlated with myocardial infarction in all experimental groups. In conclusion, the mitochondrial genome of SHR modulates the IS-limiting effect of adaptation to CNH by affecting mitochondrial energetics and MPTP sensitivity to opening.


2014 ◽  
Author(s):  
Sarah Dayle Herrmann ◽  
Jessica Bodford ◽  
Robert Adelman ◽  
Oliver Graudejus ◽  
Morris Okun ◽  
...  

2018 ◽  
Vol XIII (3) ◽  
Author(s):  
I.О. Маzunin

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