简介

We have known for many years that a large number of rare human diseases involve dysfunction of mitochondria, the energy-producing organelles in cells. More recently, we have learned that common disorders such as Parkinson disease, Alzheimer disease, diabetes and cancer all involve aspects of mitochondrial dysfunction. We are interested in how aberrant mitochondrial-nuclear communication contributes to these diseases. The Bogenhagen laboratory has had a role in defining the basic mechanisms of mitochondrial DNA (mtDNA) replication, transcription and repair in animal cells. All of the proteins involved in these critically important processes, over 200 in number, are encoded by nuclear genes whose protein products are imported into mitochondria. Our work has involved efforts to map promoters for transcription of mtDNA and to characterize mitochondrial DNA polymerase g, mtRNA polymerase, the architectural transcription factor TFAM and other accessory proteins. We were among the first to purify pol g, mtRNA polymerase and transcription factor TFBM2. In collaboration with the Kisker laboratory, we determined the crystal structure of the pol g accessory factor polgB and its relationship to the EM structure of the holoenzyme. We were also the first laboratory to reconstitute base excision repair using purified mitochondrial proteins.