Rearrangements of mitochondrial DNA (mtDNA) are a well-recognized cause of human disease; deletions are more frequent, but duplications are more readily transmitted to offspring. In theory, partial duplications of mtDNA can be resolved to partially deleted and wild-type (WT) molecules, via homologous recombination. Therefore, the yeast CCE1 gene, encoding a Holliday junction resolvase, was intr...

Mitochondria play the central role in supplying cells with ATP and are also the major source of reactive oxygen species (ROS) - molecules of both regulatory and destructive nature. Dysfunction of mitochondrial metabolism and/or morphology have been frequently reported in human cancers. This dysfunction can be associated with mitochondrial DNA (mtDNA) damage, which may be changed into mutations ...

Mitochondrial toxicity induced by nucleoside reverse transcriptase inhibitors (NRTIs) has been reported to be responsible for various adverse effects. The relative impact of NRTIs on the mitochondria of human immunodeficiency virus (HIV) type 1 (HIV-1)-infected children receiving highly active antiretroviral therapy (HAART) is unknown. Mitochondrial DNA (mtDNA) levels were quantified longitudin...

Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA) have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of thi...

The vicious cycle theory postulates that typical mitochondrial DNA (mtDNA) mutations cause their host mitochondria to generate more superoxide and other reactive oxygen species (ROS) than do normal mitochondria, thereby promoting the occurrence of additional mtDNA mutations at an everaccelerating rate. However, nearly all the loss-of-function mtDNA mutations seen in vivo are large deletions, wh...

Haematopoietic progenitor cells show special sensitivity to mitochondrial DNA (mtDNA) mutagenesis, which suggests that increased mtDNA mutagenesis could underlie anemias. Here we show that elevated mtDNA mutagenesis in mice with a proof-reading deficient mtDNA polymerase (PolG) leads to incomplete mitochondrial clearance, with asynchronized iron loading in erythroid precursors, and increased to...

Despite previously reported associations between peripheral blood mtDNA copy number and colorectal cancer, it remains unclear whether altered mtDNA copy number in peripheral blood is a risk factor for colorectal cancer or a biomarker for undiagnosed colorectal cancer. Though colorectal adenomas are well-recognized precursor lesions to colorectal cancer, no study has evaluated an association bet...

To investigate the interactions between mtDNA and nuclear genomes, we produced heteroplasmic maternal lineages by transferring the cytoplasts between the embryos of two mouse strains, C57BL/6 (B6) and RR. A total of 43 different nucleotides exist in the displacement-loop (D-loop) region of mtDNA between B6 and RR. Heteroplasmic embryos were reconstructed by electrofusion using a blastomere from...

Mitochondrial DNA (mtDNA) is vulnerable to mutations, and the number of copies of mtDNA per cell may increase to compensate for DNA damage. Case-control studies have reported associations between altered mtDNA copy number and risk of renal cell carcinoma (RCC); however, this association has not been investigated prospectively. We conducted a nested case-control study (252 cases and 504 controls...

The vicious cycle theory postulates that typical mitochondrial DNA (mtDNA) mutations cause their host mitochondria to generate more superoxide and other reactive oxygen species (ROS) than do normal mitochondria, thereby promoting the occurrence of additional mtDNA mutations at an ever-accelerating rate. However, nearly all the loss-of-function mtDNA mutations seen in vivo are large deletions, w...