The A3243G mutation in the mitochondrial gene for human mitochondrial (mt) tRNA(Leu(UUR)), responsible for decoding of UUR codons, is associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We previously demonstrated that this mutation causes defects in 5-taurinomethyluridine (taum(5)U) modification at the anticodon first (wobble) position of th...

We investigated cellular glucose uptake of fibroblast cultures derived from seven patients with mitochondrial DNA (mtDNA) A3243G mutation and from six healthy controls with no mtDNA mutations. Heteroplasmy of fibroblast cultures were shifted by culturing for 5 days in galactose-containing medium. The proportion of mutant mtDNA decreased by 7.7% to 10% in three patient fibroblast cultures, where...

Segregation of mitochondrial DNA (mtDNA) is an important underlying pathogenic factor in mtDNA mutation accumulation in mitochondrial diseases and aging, but the molecular mechanisms of mtDNA segregation are elusive. Lack of high-throughput single-cell mutation load assays lies at the root of the paucity of studies in which, at the single-cell level, mitotic mtDNA segregation patterns have been...

A 61-year-old diabetic woman with a mitochondrial A3243G mutation was hospitalized for evaluation of breathlessness, general fatigue, and leg edema. Chest radiography revealed cardiomegaly with massive pleural effusion. Serum lactate, pyruvate, and brain natriuretic peptide concentrations were elevated. Transthoracic echocardiography revealed a restrictive pattern of transmitral flow, although ...

Maternally inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. This subtype of diabetes is characterized by maternal transmission, young age at onset and bilateral hearing impairment. Besides diabetes and deafness, the main diagnostic features, a wide range of multisystemic symptoms may be associated wit...

PURPOSE It has been suggested that mitochondrial disease may be responsible for a substantial proportion of strokes of indetermined origin. We have preliminarily screened for MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) mutations in young patients with cryptogenic strokes. METHOD The mitochondrial mutations A3243G and T3271C were investigated in 38 subjec...

We describe cloned segments of rDNA that contain short type I insertions of differing lengths. These insertions represent a coterminal subset of sequences from the right hand side of the major 5kb type I insertion. Three of these shorter insertions are flanked on both sides by a short sequence present as a single copy in uninterrupted rDNA units. The duplicated segment is 7, 14 and 15 nucleotid...

Supporting analysis of “active promoter” and “enhancer” region properties We compared a number of properties of “promoter” and “enhancer” regions as defined in the main paper. We observed that both clusters contained high levels of PU.1 and C/EBPβ ChIP-seq tags, but Pol2 binding was restricted mainly to the “promoter” cluster (Supplementary Fig. 1B). CpG scores and GC content (not shown) were m...