Mitochondria are thought to have evolved from ancient prokaryotes living inside other cells as endosymbionts. One vestige of this evolutionary history is that the mitochondrial organelle still maintains and expresses its own DNA (mtDNA). Our laboratory has a long-standing and continuing interest in this extrachromosomal genome, mainly in the areas of mtDNA replication and transcription.
MtDNA encodes essential proteins involved in oxidative phosphorylation, and the production of ATP is a well-known function of the mitochondria. Therefore, mtDNA expression defects are most commonly associated with bioenergetic deficiencies. However, ATP production is not the only function of the mitochondria.
The mitochondria are also involved in a variety of signaling pathways, including apoptosis, survival, growth, development, and immune responses, among others. The details of many of these signaling pathways remain obscure. Nonetheless, it appears that the assimilation of a symbiotic prokaryote through evolutionary time has involved varied and unique mechanisms of communication between the mitochondria and other intracellular and extracellular compartments.
Some of our current research interests are at the interface between the molecular dynamics of mtDNA and extramitochondrial signaling events. MtDNA is organized within "nucleoids," which are loosely packaged bundles of mtDNA, RNA, and various proteins. Molecular signals to and from the mitochondrial genome are mediated by these various components of the nucleoid. Most of the questions in this area remain fundamental. Is the nucleoid composition homogenous, or is it tailored to local needs within a cell? Which signals are directly mediated by the nucleoid components? What subset of nucleoids is associated with the inner mitochondrial membrane or with contiguous cytoskeletal structures, where they might be better positioned for intracellular communication? We are using various fluorescently tagged proteins and the newly developed PALM imaging system in this effort (in collaboration with Eric Betzig, Janelia Farm Research Campus). The high spatial resolution provided by PALM provides a unique opportunity in this regard, since the small physical dimensions of the mitochondria have previously precluded such an analysis.
We are also exploring model systems in which to study in a more general fashion the roles of the mitochondria in synapse development, maintenance, and degeneration. This is in context with neuronal networking themes at the Janelia Farm Research Campus.