Molecular base of biochemical complex I deficiency.

The oxidative phosphorylation (OXPHOS) system, consisting of five enzyme complexes (I-V) together with 2 electron carriers, has an important role in the energy metabolism of the cell. With 45 subunits, complex I is the first and largest complex of the respiratory chain. It is under bigenomic control and a proper interaction between the mitochondrial and the nuclear genome is important for a good biogenesis and functioning of the complex.

Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile.

Putative cancer stem cells have been identified in glioblastomas and are associated with radio- and chemo-resistance. Further knowledge about these cells is thus highly warranted for the development of better glioblastoma therapies. Gene expression analyses of 11 high-grade glioma cultures identified 2 subsets, designated type A and type B cultures.

NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease.

Mitochondrial complex I deficiency is the most common defect of the oxidative phosphorylation system. We report a patient with Leigh syndrome who showed a complex I deficiency expressed in cultured fibroblasts and muscle tissue. To find the genetic cause of the complex I deficiency, we screened the mitochondrial DNA and the nuclear-encoded subunits of complex I.

Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative phosphorylation complex I.

Acyl-CoA dehydrogenase 9 (ACAD9) is a recently identified member of the acyl-CoA dehydrogenase family. It closely resembles very long-chain acyl-CoA dehydrogenase (VLCAD), involved in mitochondrial beta oxidation of long-chain fatty acids. Contrary to its previously proposed involvement in fatty acid oxidation, we describe a role for ACAD9 in oxidative phosphorylation.

Novel mutations in the NDUFS1 gene cause low residual activities in human complex I deficiencies.

Mitochondrial complex I deficiency is the most frequently encountered defect of the oxidative phosphorylation system. To identify the genetic cause of the complex I deficiency, we screened the gene encoding the NDUFS1 subunit. We report 3 patients with low residual complex I activity expressed in cultured fibroblasts, which displayed novel mutations in the NDUFS1 gene.

Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease.

Mitochondrial complex I deficiency is the most prevalent and least understood disorder of the oxidative phosphorylation system. The genetic cause of many cases of isolated complex I deficiency is unknown because of insufficient understanding of the complex I assembly process and the factors involved. We performed homozygosity mapping and gene sequencing to identify the genetic defect in five complex I-deficient patients from three different families.

Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I deficiency.

Mitochondrial complex I deficiency is the most common defect of the OXPHOS system. We report a patient from consanguineous parents with a complex I deficiency expressed in skin fibroblasts. Homozygosity mapping revealed several homozygous regions with candidate genes, including the gene encoding an assembly factor for complex I, NDUFAF2.

NDUFA2 complex I mutation leads to Leigh disease.

Mitochondrial isolated complex I deficiency is the most frequently encountered OXPHOS defect. We report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Because the parents were consanguineous, we performed homozygosity mapping to identify homozygous regions containing candidate genes such as NDUFA2 on chromosome 5.