Mitochondrial DNA defects were established as a cause of human disease over 20 years ago, and they are increasingly recognized as a contributory factor in major causes of human morbidity, such as neurodegeneration. Although mitochondrial DNA is known to be packaged with a variety of proteins, their functions are in many cases ill defined; hence this field is in its infancy. The functional characterization of DNA transacting proteins in mitochondria is critical to a full understanding of mitochondrial DNA metabolism and the human diseases that result when mitochondrial DNA is mutated. The proposed host laboratory is well recognized for high quality and innovative research in the field of mitochondrial genetics, and it has recently demonstrated that two components of the actin cytoskeleton are present inside mitochondria, where they associate with mitochondrial DNA. The planned experiments on these two proteins, will examine their role in mitochondrial DNA movement and transmission, identify protein partners and investigate a disease mouse model; collectively they aim to develop this new area of cell biology and determine the role of the ‘mitoskeleton’ in mitochondrial DNA maintenance and mitochondrial function.