Deficiency of the voltage-dependent anion channel: a novel cause of mitochondriopathy.

A patient with a deficient voltage-dependent anion channel (VDAC) is reported, presenting clinically with psychomotor retardation and minor dysmorphic features. Biochemical studies on muscle mitochondria showed impaired rates of pyruvate oxidation and ATP production; however, no specific deficient activity of one of the mitochondrial enzymes was involved. Western blotting experiments indicated an almost complete VDAC deficiency in skeletal muscle.

Importance of mitochondrial transmembrane processes in human mitochondriopathies.

In a substantial group of subjects suspected to have a mitochondriopathy no defect in the mitochondrial energy metabolism (pyruvate dehydrogenase complex or respiratory chain complexes) can be demonstrated. At least in some of these subjects it seems justified to consider a defect in one of the proteins which mediate the transport of several ions and substrates across the mitochondrial membranes. Of particular interest are proteins which are directly involved in the process of oxidative phosphorylation, such as the adenine nucleotide translocator (ANT) and the phosphate carrier (PiC).