OBJECTIVE Cytochrome c oxidase (COX) deficiency has been demonstrated in some patients with Alpers-Huttenlocher disease, but no genetic background has been identified. Our objective was to determine the molecular defect underlying the mitochondrial respiratory chain deficiency in a child with Alpers-Huttenlocher-like progressive cerebrohepatic disease. METHODS The entire coding region of mito...

Analysis of mitochondrial DNA control region sequences from 41 species of bats representing 11 families revealed that repeated sequence arrays near the tRNA-Pro gene are present in all vespertilionine bats. Across 18 species tandem repeats varied in size from 78 to 85 bp and contained two to nine repeats. Heteroplasmy ranged from 15% to 63%. Fewer repeats among heteroplasmic than homoplasmic in...

Human TP53 gene is characterised by a polymorphism at codon 72 leading to an Arginine-to-Proline (R/P) substitution. The two resulting p53 isoforms have a different subcellular localisation after stress (more nuclear or more mitochondrial for the P or R isoform, respectively). p53P72 variant is more efficient than p53R72 in inducing the expression of genes involved in nuclear DNA repair. Since ...

Mutations in the mitochondrial DNA (mtDNA) can cause a variety of human diseases. In most cases, such mutations are heteroplasmic (i.e. mutated and wild-type mtDNA coexist) and a small percentage of wild-type sequences can have a strong protective effect against a metabolic defect. Because a genetic approach to correct mtDNA mutations is not currently available, the ability to modulate heteropl...

The pathogenesis of sporadic Parkinson's disease (PD) remains enigmatic. Mitochondrial complex-I defects are known to occur in the substantia nigra (SN) of PD patients and are also debated in some extracerebral tissues. Early sequencing efforts of the mitochondrial DNA (mtDNA) did not reveal specific mutations, but a long lasting discussion was devoted to the issue of randomly distributed low l...

Exchange of homologous sequences between mitochondrial DNA (mtDNA) molecules is thought to be absent in animals, primarily because of a failure to observe clear cases of recombinant haplotypes in natural populations. However, whether mtDNA recombination occurs is a different issue from whether it produces new haplotypes. A requirement for the latter is heteroplasmy – the presence of more than o...

It is now well established that, even within a single cell, multiple copies of the mitochondrial genome may be present (genetic heteroplasmy). It would be interesting to develop techniques to determine if and to what extent this genetic variation results in functional variation from one mitochondrion to the next (functional heteroplasmy). Measuring mitochondrial respiration can reveal the organ...

Mutations in mitochondrial DNA (mtDNA) may cause maternally-inherited cardiomyopathy and heart failure. In homoplasmy all mtDNA copies contain the mutation. In heteroplasmy there is a mixture of normal and mutant copies of mtDNA. The clinical phenotype of an affected individual depends on the type of genetic defect and the ratios of mutant and normal mtDNA in affected tissues. We aimed at deter...