Research focus



Fundamentals of biochemical and genetic defects of the energy metabolism

This project understands itself as continuation of the routine diagnostics about defects in the mitochondrial energy metabolism. Special biochemical methods for the detection of enzymatic defects increases the rate of specific diagnosis. The localisation of the genetic defects and the understanding of molecular mechanisms of the diseases are the basis for possible therapies.


Methodical improvement of mitochondrial diagnostics

The scale down of the assays should lead to a dramatic reduction of tissue necessary for biochemical diagnostics. This is especially important for sampling of tissue of neonates and by needle biopsy. The comparison of two procedures for the functional investigation of native mitochondria will reveal the most predictive method in routine diagnostics of defects of the mitochondrial energy metabolism.

High throughput screening for mutations of the mitochondrial DNA

Mutations of the mitochondrial DNA are the most common reason for a defect of the respiratory chain. The aim of the project is to establish a sensitive, cost-efficient screening procedure for the detection of pathological mutations in patients with biochemically proven defect of the mitochondrial energy metabolism.


Energy metabolism in neoplasia

There is increasing evidence that mtDNA alterations also occur frequently in various tumors. To gain further information on somatic mtDNA mutations in different types of pediatric tumors the entire mtDNA genome will be screened in various tumor samples. The mechanism beyond and the patho-physiological relevance of somatic mtDNA mutations in cancer are not clear and diversely discussed. Only alterations of mtDNA which have an effect on energy metabolism should have the potential to be pathologically significant for tumor development. Therefore, the effect of mtDNA alterations on OXPHOS capacity will be investigated in different types of tumors.






Molecular genetic screening of complex I defects

The complex I defect is one of the most common respiratory chain defects. However, the identification of disease-related genes is still at an early stage. This is also due to the multiplicity of complex I structural genes. In this project, patients with isolated complex I defect are screened for mutations of all complex I structural genes, using ‘high-throughput’ analytical methods.

Intergenomic communication defects

The synthesis of mitochondrial DNA (mtDNA) is regulated by various enzymes. Defects in one of these enzymes lead to a disruption in the functioning of the respiratory chain and thus to mitochondrial disorders. As of late, at least six nuclear genes have been detected (DGUOK, POLG1, TP, TK2, SUCLA2, MPV 17), the mutations of which lead to mtDNA defects (depletion/multiple deletion). It is advised that patients with a hitherto undetected mtDNA depletion or deletion gene defect undergo mutation screening for these and other candidate genes.

Molecular diagnostics and therapy for coenzyme Q10 defects

Congenital deficiencies of coenzyme Q10 (CoQ10) lead to respiratory chain defects. Patients with respiratory chain defects of unclear genesis and a decrease in CoQ10 muscular content should undergo molecular screening of genes which are involved in the CoQ10 metabolism. The effect of CoQ10 replacement therapy will continue to be evaluated in vitro and in vivo.


The Salzburg projects are funded by:

Jubiläumsfond der Oesterreichischen Nationalbank
   Projekte 8314 und 10131
Salzburger Kinderkrebshilfe
• Vereinigung zur Förderung Pädiatrischer Forschung und
   Fortbildung Salzburg
Österreichisches Grünes Kreuz
Aktion Österreich – Tschechische Republik
   Projekte II.-12 und 2001-20