Laura Lackner Spatial organization within cells, using mitochondrial structure & distribution as a model
Research Interests
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. The position of one organelle cannot be studied in isolation as organelles make physical and functional contact with other organelles. These sites of contact, known as membrane contact sites (MCSs), have been identified between every organelle pair tested and play critical roles in spatially organizing cells and facilitating the transfer of biological materials between organelles.
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 tethering plays a critical role in mitochondrial positioning, interorganelle contact, and, consequently, cellular function in cells from yeast to neurons, the molecular mechanisms and functions are poorly understood.
Using cell biology, genetics, biochemistry, and synthetic biology approaches, we are addressing fundamental questions about the tethering mechanisms used by cells to position mitochondria as well as form and regulate MCSs: 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?
Selected Publications
Mitochondria-ER-PM contacts regulate PI(4)P distribution and mitochondrial division. Casler JC, Harper CS, White AJ, Anderson HL, and Lackner LL. (2024) Mitochondria-ER-PM contacts regulate PI(4)P distribution and mitochondrial division. Journal of Cell Biology. 223:e202308144.
Temporal control of contact site formation reveals a relationship between mitochondrial division and Num1-mediated mitochondrial tethering. Harper CS, Casler JC, and Lackner LL. (2023) Molecular Biology of the Cell 34:ar108.
Loss of Num1-mediated cortical dynein anchoring negatively impacts respiratory growth. White AJ, Harper CS, Rosario EM, Dietz JV, Addis HG, Fox JL, Khalimonchuk O, and Lackner LL. Journal of Cell Science. 2022 135 (21): jcs259980.
Hierarchical integration of mitochondrial and nuclear positioning pathways by the Num1 EF hand. Anderson HL, Casler JC, and Lackner LL. Molecular Biology of the Cell. 2022 February 1;33(2):ar20.
The multifunctional nature of mitochondrial contact site proteins. Harper CS, White AJ, and Lackner LL. Current Opinion in Cell Biology. 2020 August;65:58-65.
View all publications by Laura L. Lackner listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.