We are interested in understanding how spatial organization within cells is achieved. As a model for intracellular organization, we study how mitochondria are shaped and positioned within cells. The shape and position of mitochondria depend on the integrated and regulated activities of mitochondrial division, fusion, motility, and tethering. These activities govern the overall connectedness, shape and location of mitochondria within cells and consequently influence both mitochondrial and cellular function. Both the shape and position of mitochondria are highly dynamic and vary by cell type, developmental stage and physiological context. Thus, the activities of mitochondrial division, fusion, motility, and tethering must be coordinated to properly shape and position mitochondria in response to the changing needs of the cell.
Of the activities that contribute to the shape and position of the mitochondrial network, the least is known about the molecular mechanisms underlying the tethering of mitochondria to specific cellular sites. To fill this gap in knowledge, we have focused our efforts on the characterization of mitochondrial tethers required for proper mitochondrial positioning in yeast. Using multidisciplinary biochemical, cytological and genetic approaches that take advantage of the facile yeast system, we are working to elucidate the molecular basis and physiological significance of these mitochondrial tethers and address how their activities are regulated and integrated with other pathways, such as lipid homeostasis and stress responses, to maintain cellular homeostasis. Interestingly, the mitochondrial tethers required for proper mitochondrial positioning in yeast associate with the ER, and we hypothesize that the ER will have a critical and conserved role in mitochondrial tethering in many cell types.
Num1 anchors mitochondria to the plasma membrane via two domains with different lipid binding specificities. Ping HA, Kraft LM, Chen W, Nilles AE, and Lackner LL. Journal of Cell Biology. 2016 June 6;213(5):513-524.
Shaping the dynamic mitochondrial network. Lackner LL. BMC Biology. 2014 May 27;12:35.
Determining the shape and cellular distribution of mitochondria: the integration of multiple activities. Lackner LL. Current Opinion in Cell Biology. 2013 August;25(4):471-476.
Endoplasmic reticulum-associated mitochondria–cortex tether functions in the distribution and inheritance of mitochondria. Lackner LL, Ping H, Graef M, Murley A, and Nunnari J. PNAS. 2013 February 5;110(6):E458-E467.
ER Tubules Mark Sites of Mitochondrial Division. Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, and Voeltz GK. Science. 2011 October 21;334(6054):358-362.
A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria. Hoppins S, Collins SR, Cassidy-Stone A, Hummel E, DeVay RM, Lackner LL, Westermann B, Schuldiner M, Weissman JS, and Nunnari J. Journal of Cell Biology. 2011 October 17;195(2):323-340.
Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Mears JA, Lackner LL, Fang S, Ingerman E, Nunnari J, and Hinshaw JE. Nature Structural & Molecular Biology. 2011 January;18(1):20-26.
Small Molecule Inhibitors of Mitochondrial Division: Tools that Translate Basic Biological Research into Medicine. Lackner LL and Nunnari J. Chemistry & Biology. 2010 June 25;17(6):578-583.
The molecular mechanism and cellular functions of mitochondrial division. Lackner LL and Nunnari JM. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2009 December;1792(12):1138-1144.
Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion. DeVay RM, Dominguez-Ramirez L, Lackner LL, Hoppins S, Stahlberg H, and Nunnari J. Journal of Cell Biology. 2009 September 21;186(6):793-803.
Mechanistic Analysis of a Dynamin Effector. Lackner LL, Horner JS, and Nunnari J. Science. 2009 August 14;325(5942):874-877.
The Machines that Divide and Fuse Mitochondria. Hoppins S, Lackner L, and Nunnari J. Annual Review of Biochemistry. 2007 July;76:751-780.
View all publications by Laura L. Lackner listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.