Mitochondrial respiratory chain (RC) deficiency is among the most common causes of inherited metabolic disease, but its physiological consequences are poorly characterized. We studied the skeletal muscle gene expression profiles of mice with late-onset mitochondrial myopathy. These animals express a dominant patient mutation in the mitochondrial replicative helicase Twinkle, leading to accumula...

During the last decade, disorders of the respiratory chain, socalled mitochondrial disorders, have emerged as a major clinical entity. Though Leigh’s disease, also known as Subacute Necrotizing Encephalomyelopathy, has been mostly reported in infancy and childhood, it is described in adults [1]. Leigh's disease is a myopathy causing degradation of motor skills with occasional cardiac involvemen...

Abnormal left ventricular trabeculations can be a cardiac manifestation of Becker’s muscular dystrophy. Abnormal left ventricular trabeculations in mitochondrial myopathy have not been reported before. A 68 year old man with a history of chronic congestive heart failure and hypertension, had recurrent raised creatine kinase (CK) concentrations (up to 150 U/l; normal 70 U/l) with normal CKMB iso...

McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically mini...

An uncommon but increasingly diagnosed clinical situation in humans is mitochondrial myopathy, a condition in which muscle function is impaired by defective mitochondrial metabolism in the generation of energy for muscle contraction. It is also now clear that abnormalities of mitochondrial function are not limited to muscle, but may also underlie multisystem disease, in which other tissues are ...

Hereditary inclusion body myopathy (HIBM) is an adult onset, slowly progressive distal and proximal myopathy. Although the causing gene, GNE, encodes for a key enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains unknown. To elucidate the pathological mechanisms leading from the mutated GNE to the HIBM phenotype, we attempted to identify and characterize early occurri...

Adenine nucleotide translocase (Ant) is the most abundant protein on the mitochondrial inner membrane (MIM) primarily involved in ADP/ATP exchange. Ant also possesses a discrete membrane uncoupling activity. Specific mis-sense mutations in the human Ant1 cause autosomal dominant Progressive External Ophthalmoplegia (adPEO), mitochondrial myopathy and cardiomyopathy, which are commonly manifeste...

Many kinds of mutations in mitochondrial (mt) DNA have been reported to be related to the development of Diabetes Mellitus (DM), this type of diabetes has also been shown to be influenced by other genetic factors and/or environmental factors. Among them, tRNALeu(UUR) and its adjacent mtDNA NADH dehydrogenase subunit 1(ND1) region within the mt genome are linked to high susceptibility to DM. A p...

Muscle contraction relies on a highly organized intracellular network of membrane organelles and cytoskeleton proteins. Among the latter are the intermediate filaments (IFs), a large family of proteins mutated in more than 30 human diseases. For example, mutations in the DES gene, which encodes the IF desmin, lead to desmin-related myopathy and cardiomyopathy. Here, we demonstrate that myotubul...

BACKGROUND Myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome typically manifests in adults younger than 40 years with encephalopathy, stroke-like episodes, and lactic acidosis. Magnetic resonance imaging (MRI) abnormalities typically involve the cortical gray and the adjacent subcortical white matter. OBJECTIVE To describe a 58-year-old woman diagnosed with ...