A mitochondrial matrix-specific p53 construct (termed p53-290) in HepG2 cells was utilized to determine the impact of p53 in the mitochondrial matrix following oxidative stress. H2O2 exposure reduced cellular proliferation similarly in both p53-290 and vector cells, and p53-290 cells demonstrating decreased cell viability at 1 mM H2O2 (~ 85% viable). Mitochondrial DNA (mtDNA) abundance was decreased in a dose-dependent manner in p53-290 cells while no change was observed in vector cells. Oximetric analysis revealed reduced maximal respiration and reserve capacity in p53-290 cells. Our results demonstrate that mitochondrial matrix p53 sensitizes cells to oxidative stress by reducing mtDNA abundance and mitochondrial function.

Case 1: 12 year old girl, 2nd of 4 children of consanguineous Iraqi parents with bilateral, dyskinetic, spastic paresis. Until 4 years of age normal development, than increasing tremor and dystonia, rigor and spasticity of the lower, later of the upper extremities. Progressively scoliosis, loss of gait, loss of speech, hypertrophic cardiomyopathy and symptomatic epilepsy developed. Therapy with intrathecal Baclofen slightly stabilized the situation.

Nearly all patients affected by myoclonic epilepsy with ragged-red fibres (MERRF) harbour a mutation in the mitochondrial transfer RNA(Lys) gene. We report on an 8-year-old girl with clinical and diagnostic features of MERRF. After excluding one of the common mutations associated with MERRF, a complete sequence analysis of the mitochondrial genome revealed an m.4284 G > A mutation in the mitochondrial transfer RNA(Ile) gene. This mutation has only once been described in a family with variable clinical symptoms, but has not yet been linked to MERRF. This case extends the mutational spectrum associated with the MERRF phenotype, and demonstrates the importance of performing a comprehensive mutational analysis in patients with suspected mitochondrial disease when common mutations have been ruled out.

The STREAM-EU model was used to predict the water concentrations, estuarine export and retention of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in the eleven most populated European river catchments to provide a European-wide perspective on the contamination by these substances.Emissions of PFOS and PFOA to those catchments were calculated based on population, wealth and wastewater treatment plant (WWTP) coverage and efficiency using a previously published method and used as model input. Our estimated emissions showed the lowest values for the Thames catchment (PFOS: 0.4 ton/y; PFOA: 0.2 ton/y) and the highest values for the Rhine for PFOS (1.6 ton/y) and for the Dnieper for PFOA (1.7 ton/y).The model predicted concentrations agreed reasonable well with the existing range of measurements, apart from for PFOA in the River Po, where there is a known historical industrial contamination, and PFOS in the Rhone River, where results were much higher than the few measurements available. It was concerning that the model predicted that the surface water EQS for PFOS (0.65 ng/L) was exceeded by a wide margin in all the eleven studied European river catchments.The total calculated riverine export to the seas from the eleven catchments was 4.5 ton/y of PFOS and 3.7 ton/y of PFOA with highest exported quantities from the Rhine (PFOS: 1.0 ton/y; PFOA: 1.0 ton/y) and Danube estuaries (PFOS: 0.9 ton/y; PFOA: 0.7 ton/y). For the seas where the rivers discharge, riverine discharge of PFOS was estimated to be 2.5–30 times more important as an input than atmospheric deposition, whereas for PFOA the opposite was true (atmospheric deposition was 2–10 times more important) except for very small seas.

Complex I (C I) deficiency is a frequent cause (30%) of pediatric mitochondrial disease, presenting with a phenotypic spectrum from lethal multisystem disorder to mild myopathy. More than 80% of the patients present neurologic symptoms. The diagnosis is based on biochemical analysis of C I-activity in muscle or fibroblasts. The molecular diagnosis is difficult to establish due to a large number of candidate genes (>80). Therefore prognostic evaluation, genetic counseling, prenatal diagnosis and also therapeutic approaches are difficult.

This is the case of a 41 year old man, suffering general weakness and elevated liver enzymes, sensitive to a treatment with riboflavin and coenzyme Q(10). Tandem mass spectroscopy and molecular analysis reveal a multiple acyl-CoA-dehydrogenase deficiency (MADD) with two novel heterozygote missense mutations of the EFTDH gene.

Pregnancy, birth and postnatal course were uneventful in all cases. One girl presented very early with a primary developmental delay, 2 children presented in the first year of life, 2 further children in the second year of life. Initial symptoms were in all cases a muscular hypotonia, ataxia, feeding difficulties, whereas metal and speech development were much better. 2 children present with a tachypnoea due to central lactatacidosis. Labatory tests showed lactic acidosis in plasma in some but not all samples however increased lactate in CSF was demonstrated in all cases. Muscle morphology showed no characteristic results. The analysis of the respiratory chain complexes showed severe COX-deficiency in all cases. Pathogenic mutations in the SURF1 gen could be found in all cases. Initial MRI-scans revealed in 4/5 cases typical symmetrical signal changes of variable intensity, in one case the initial MRT was normal and shows a Leigh-like picture in the course of the disease. None of the children had cardiac problems. Clinical all children show a progressive muscular hypotonia, ataxia and recurrent episodes of vomiting and regression. Frequency and intensity of these episodes were variable and partly very severe. Need for artificial ventilation was in 2 cases, 2 children show a benign course, one girl is able to walk with aid.

Isolated mitochondrial complex I (CI) deficiency accounts for about one third of respiratory chain disease, which collectively has an incidence of 1 in 5,000 live births.

The Center of Metabolic Disease Klinikum Schwabing investigates patients with suspicion of mitochondrial disease for now more than twenty years. Since at least ten years genetic diagnosis gets more and more important for this field. We present conclusions from the statistical analysis of samples investigated within the last five years (1.1.2005–31.12.2009).