A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.

Glutaric aciduria type I (GA-I, OMIM # 231670) is an autosomal recessive inborn error of metabolism caused by deficiency of the mitochondrial enzyme glutaryl-CoA dehydrogenase (GCDH). The principal clinical manifestation in GA-I patients is striatal injury most often triggered by catabolic stress. Early diagnosis by newborn screening programs improved survival and reduced striatal damage in GA-I patients.

The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.

Glutaric aciduria type I (GA-I, OMIM # 231670) is an inborn error of metabolism caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH). Patients develop acute encephalopathic crises (AEC) with striatal injury most often triggered by catabolic stress. The pathophysiology of GA-I, particularly in brain, is still not fully understood.

Case Report and Review of the Literature: A New and a Recurrent Variant in the Gene Are Associated With Isolated Lethal Hypertrophic Cardiomyopathy, Hyperlactatemia, and Pulmonary Hypertension in Early Infancy.

Mitochondriopathies represent a wide spectrum of miscellaneous disorders with multisystem involvement, which are caused by various genetic changes. The establishment of the diagnosis of mitochondriopathy is often challenging. Recently, several mutations of the gene encoding the mitochondrial valyl-tRNA synthetase were associated with early onset encephalomyopathies or encephalocardiomyopathies with major clinical features such as hypotonia, developmental delay, brain MRI changes, epilepsy, hypertrophic cardiomyopathy, and plasma lactate elevation.

Low VDAC1 Expression Is Associated with an Aggressive Phenotype and Reduced Overall Patient Survival in Cholangiocellular Carcinoma.

Cancer cells frequently exhibit dysfunctional oxidative phosphorylation (OXPHOS) and a concomitant increase in glycolytic flux. We investigated the expression of OXPHOS complex subunits and mitochondrial mass in 34 human cholangiocellular carcinomas (CCCs) and adjacent normal tissue by using tissue microarrays. In the tumor periphery, all OXPHOS complexes were reduced except complex I.

A ketogenic diet supplemented with medium-chain triglycerides enhances the anti-tumor and anti-angiogenic efficacy of chemotherapy on neuroblastoma xenografts in a CD1-nu mouse model.

Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction in aerobic energy metabolism. Recent preclinical data indicate that targeting this metabolic phenotype by a ketogenic diet (KD), especially in combination with calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide (CP) therapy of NB xenografts. Because calorie restriction would be contraindicated in most cancer patients, the aim of the present study was to optimize the KD such that the tumors are sensitized to CP without the need of calorie restriction.

Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

Introduction: Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer's oxidative phosphorylation system.

TMEM70 deficiency: long-term outcome of 48 patients.

Objectives: TMEM70 deficiency is the most common nuclear-encoded defect affecting the ATP synthase. In this multicentre retrospective study we characterise the natural history of the disease, treatment and outcome in 48 patients with mutations in TMEM70. Eleven centers from eight European countries, Turkey and Israel participated.

Alterations of oxidative phosphorylation complexes in astrocytomas.

The shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, even under aerobic conditions, called the Warburg effect, is a feature of most solid tumors. The activity levels of OXPHOS complexes and citrate synthase were determined in astrocytomas. A gradual decrease of citrate synthase and OXPHOS complexes was observed depending on tumor grade.