Our research program seeks to address the fundamental biological question of how spatial and dynamic organization within cells is achieved. The positioning of cellular components in the right place at the right time is a highly choreographed, complex process that is critical for cellular function. As a model for intracellular organization, we study the mechanisms that position organelles. While once thought to operate independently, it is clear that organelles contact other organelles, and the positioning of organelles and the contacts they make play critical roles in a wide variety of cellular functions.
The organelle that has been the primary focus of our research is the mitochondrion, which is best known for its role in energy production. Mitochondria also participate in many other biological processes that are important for cellular function such as producing critical cellular building blocks and contributing to cell life and death decision pathways. Mitochondria form highly dynamic, interconnected tubular networks in a majority of cell types. The positioning of this complex network relative to the overall structure of the cell and to other organelles within the cell is critical for both organellar and cellular function. Central to mitochondrial positioning and the interorganelle contacts mitochondria make are molecular tethers. While tethers play critical roles in mitochondrial positioning, interorganelle contact, and, consequently, cellular function in cells from yeast to neurons, the molecular mechanisms are poorly understood, and we are working to address this deficit.
Using a combination of cell biological, genetic, and biochemical approaches, we are addressing fundamental questions about the tethering mechanisms used by cells to position mitochondria as well as form and regulate interorganelle contacts:
1) What are the molecular bases and mechanisms of mitochondrial tethering?
2) How is tethering spatially and temporally regulated?
3) How does tethering impact organelle and cellular function?
4) What are the additional functions of tethers that have yet to be described?