Maintaining the human mitochondrial genome

Mitochondria in eukaryotes constitute a dynamic network that is continuously fusing and dividing. This network is the main producer of cellular ATP, the energy currency used for a variety of metabolic reactions.

New mitochondria are formed based on genetic information from two different sources, the nuclear genome and mitochondrial DNA.

The mtDNA encodes only 13 proteins and these are all subunits of the oxidative phosphorylation (OXPHOS) system, whereas nuclear genes encode the remaining ~100 proteins needed for mitochondrial function.

The overall goal of my research is to understand the basic, molecular mechanisms of mitochondrial DNA (mtDNA) replication in mammalian cells. An essential part of this work is to study disease-causing mutations affecting mtDNA replication factors.

More than 300 such mutations have been identified in the mitochondrial DNA polymerase and we investigate how specific mutations cause distinct biochemical defects in affected patients. We frequently collaborate with clinicians to verify the causative effects of suspected disease-causing mutations.

We also work to develop unique mouse models and new therapeutic approaches for this heterogenous group of diseases.specific aims:Aim 1. To establish how non-coding 7S RNA regulates transcription and mtDNA replication.Aim 2. To elucidate why different disease-causing mutations, cause distinct mtDNA aberrations.Aim 3.

To use reverse genetics to establish new mouse models for mtDNA deletion diseases.