Name: Dan F. Bogenhagen

Position: Professor Of Pharmacology

Research Description:

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.

In recent years we have sought to understand the macromolecular environment in which these proteins function within mitochondria. MtDNA is not packaged in nucleosomes, but resides in tightly packed nucleoids associated with the mitochondrial inner membrane. These nucleoids are fundamental units for inheritance of mtDNA-encoded diseases. We have used super-resolution microscopy to study the structure of nucleoids and facilitated efforts to bring this innovative technology to Stony Brook University. We have used proteomics to identify proteins associated with mtDNA nucleoids. MtDNA replication, transcription, and RNA processing events are all controlled at nucleoids serving as major centers for mitochondrial biogenesis. Most recently we have expanded this work to show that the initial steps in mitochondrial ribosome biogenesis occur at the nucleoid as newly-synthesized mitochondrial ribosomal proteins first bind nascent mitochondrial ribosomal RNA while it is still being transcribed form the mtDNA. Our current research explores the coordination of nuclear and mitochondrial genetic events at nucleoids in diverse cell types in healthy and diseased states.

Lab Memberships

Bogenhagen Lab (Principal Investigator/Director)

Contact Information

Address:
Dept. of Pharmacology
SUNY at Stony Brook
Stony Brook, NY
11794-8651, USA

Email: daniel.bogenhagen@stonybrook.edu
Web Page: http://daniel.bogenhagen@stonybrook.edu
Phone:  516 444 3068
Fax:  516 444 3218