A number of human diseases are caused by inherited mitochondrial DNA mutations. Two of these diseases, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fibres), are commonly caused by point mutations to tRNA genes encoded by mitochondrial DNA. Here we report on how these mutations affect mitochondrial function ...

It is well known that muscular dystrophy disease severity controlled by genetic modifiers. The expectation identifying these modifiers, we can illuminate additional therapeutic targets with which to combat the disease. To this end have been investigating MRL mouse strain, highly resistant dystrophy-mediated fibrosis. strain contains two mitochondrial-encoded, naturally occurring heteroplasmies:...

We report on pancreatic exocrine dysfunction in families that have the mitochondrial tRNA(Leu)(UUR) gene mutation. These families exhibited maternally inherited diabetes mellitus (DM) and an A to G substitution at nt 3243 of the mitochondrial tRNA(Leu)(UUR) gene (A3243G mutation). Pancreatic necropsy samples from one proband showed accumulation of degenerated mitochondria in pancreatic acinar c...

Communication between the mitochondrial and nuclear genomes is vital for cellular function. The assembly of mitochondrial enzyme complexes, which produce the majority of cellular energy, requires the coordinated expression and translation of both mitochondrially and nuclear-encoded proteins. The joint genetic architecture of this system complicates the basis of mitochondrial diseases, and mutat...

Communication between the mitochondrial and nuclear genomes is vital for cellular function. The assembly of mitochondrial enzyme complexes, which produce the majority of cellular energy, requires the coordinated expression and translation of both mitochondrially and nuclear-encoded proteins. The joint genetic architecture of this system complicates the basis of mitochondrial diseases, and mutat...

BACKGROUND Coronary heart disease is the leading cause of death worldwide. Mitochondrial genetic determinants for the development of this disorder remain less explored. METHODS AND RESULTS We performed a clinical and genetic evaluation and mutational screening of 22 mitochondrial tRNA genes in a cohort of 80 genetically unrelated Han Chinese subjects and 125 members of 4 families with coronar...

Mutations in mitochondrial DNA are an important cause of human disease and from a therapeutic standpoint, these disorders are currently untreatable. New studies now show that a non‐cognate mitochondrial aminoacyl tRNA synthetase can overcome the respiratory defect caused by an mt‐tRNA mutation and that the isolated carboxy‐terminal domain of human mt‐leucyl tRNA synthetase can ameliorate the pa...

PURPOSE To analyze mitochondrial DNA (mt DNA) gene mutations in a 19-year-old female patient, who presented with chronic progressive external ophthalmoplegia (CPEO), together with her mother and younger sister. METHODS The diagnosis of mitochondrial myopathy was made based on clinical and biologic analysis. Histochemical methods were used to detect ragged-red fibers (RRFs) and ragged-blue fib...

Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNA(Leu(UUR)). The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like epis...

RATIONALE Despite maternal transmission of hypertension in some pedigrees, pathophysiology of maternally inherited hypertension remains poorly understood. OBJECTIVE To establish a causative link between mitochondrial dysfunction and essential hypertension. METHOD AND RESULTS A total of 106 subjects from a large Chinese family underwent clinical, genetic, molecular, and biochemical evaluatio...