Mitochondrial disease associated with complex I (NADH-CoQ oxidoreductase) deficiency.

Mitochondrial diseases due to a reduced capacity for oxidative phosphorylation were first identified more than 20 years ago, and their incidence is now recognized to be quite significant. In a large proportion of cases the problem can be traced to a complex I (NADH-CoQ oxidoreductase) deficiency (Phenotype MIM #252010). Because the complex consists of 44 subunits, there are many potential targets for pathogenic mutations, both on the nuclear and mitochondrial genomes. Surprisingly, however, almost half of the complex I deficiencies are due to defects in as yet unidentified genes that encode proteins other than the structural proteins of the complex. This review attempts to summarize what we know about the molecular basis of complex I deficiencies: mutations in the known structural genes, and mutations in an increasing number of genes encoding "assembly factors", that is, proteins required for the biogenesis of a functional complex I that are not found in the final complex I. More such genes must be identified before definitive genetic counselling can be applied in all cases of affected families

Assembling Complex I with ACAD9

Acyl-Co dehydrogenase 9 (ACAD9) was thought to play a role in fatty acid oxidation. Nouws et al. (2010) reveal a novel and essential role for this enzyme in mitochondrial complex I assembly. A mutation in ACAD9 causes an isolated complex I deficiency in a subset of patients with mitochondrial disease

Assembling complex I with ACAD9.

Acyl-Co dehydrogenase 9 (ACAD9) was thought to play a role in fatty acid oxidation. Nouws et al. (2010) reveal a novel and essential role for this enzyme in mitochondrial complex I assembly. A mutation in ACAD9 causes an isolated complex I deficiency in a subset of patients with mitochondrial disease

Mitochondrial disease associated with complex I (NADH-CoQ oxidoreductase) deficiency.

Mitochondrial diseases due to a reduced capacity for oxidative phosphorylation were first identified more than 20 years ago, and their incidence is now recognized to be quite significant. In a large proportion of cases the problem can be traced to a complex I (NADH-CoQ oxidoreductase) deficiency (Phenotype MIM #252010). Because the complex consists of 44 subunits, there are many potential targets for pathogenic mutations, both on the nuclear and mitochondrial genomes. Surprisingly, however, almost half of the complex I deficiencies are due to defects in as yet unidentified genes that encode proteins other than the structural proteins of the complex. This review attempts to summarize what we know about the molecular basis of complex I deficiencies: mutations in the known structural genes, and mutations in an increasing number of genes encoding "assembly factors", that is, proteins required for the biogenesis of a functional complex I that are not found in the final complex I. More such genes must be identified before definitive genetic counselling can be applied in all cases of affected families