Molecular genetics

Mitochondrial genetics

Mitochondrial disorders are often fatal multisystem disorders, associated with abnormalities of the terminal component of mitochondrial energy metabolism, i.e. oxidative phosphorylation (OXPHOS). The objective is to foster research into the understanding of function, regulation and structure of mitochondria as vital organelles, thereby providing insight into diagnostics and treatments of diseases related to mitochondrial dysfunction. During the last ten years the Radboud Center for Mitochondrial Medicine (RCMM) has identified numerous mutations in the nuclear DNA responsible for defects in the mitochondrial energy generating capacity. However, for only a small part of the mitochondrial disorders the genetic defect has been established. Therefore ongoing research projects still aim at the discovery of new nuclear genes involved in OXPHOS diseases and the development of novel technologies (mutation chips, microarray, proteomics) to study genetic abnormalities in patients affected with a mitochondrial disorder.

The main scientific objectives are:

i.) The identification of new genes responsible for isolated complex I deficiency and combined OXPHOS complex deficiencies;
ii.) Investigation of the cell biological consequences of OXPHOS deficiencies.

The main technological objectives are:

i.) The development of high through-put genetic strategies to overcome current limitations in screening huge numbers of genes;
ii.) The development of bioinformatics to identify novel nuclear genes and pathogenic mutations responsible for mitochondrial disorders.