469362 Quantifying Intracellular Mitochondrial Dynamics Based on Cytoplasmic Electrophysiology
469362 Quantifying Intracellular Mitochondrial Dynamics Based on Cytoplasmic Electrophysiology
Monday, November 14, 2016: 9:45 AM
Embarcadero (Parc 55 San Francisco)
Mitochondria, which serve as energy centers within the cell, undergo constant fusion and fission, thereby allowing the cell to quickly adapt to environmental conditions for promoting mitochondrial health. Mutation and aberrant regulation of the mitochondrial machinery is associated with a number of human diseases including Parkinson’s Disease, Alzheimer’s Disease and Diabetes, as well as physiological processes whose dysregulation are classical hallmarks of human cancer. In recent work, we demonstrated that the activation of mitochondrial fission is required for tumor growth in a xenograft model of pancreatic cancer and inhibition of mitochondrial fission was shown to prevent tumor growth [1]. However, therapies targeting aberrant regulation of mitochondrial machinery require label-free means to quantify the dynamic alterations in mitochondrial morphology after particular genetic screens as well as towards enabling the collection live cells with a particular mitochondrial structure for downstream analysis to understand the signaling pathways. Herein, utilizing two different cell types, namely mouse embryonic fibroblasts and human embryonic kidney cells to create modified mitochondrial phenotypes by entirely independent means, we show that variations in the intracellular cytoplasmic conductivity can serve as a means for quantifying alterations in mitochondrial structure after particular genetic screens. This difference in cytoplasmic conductivity is shown to be capable of enabling frequency-selective dielectrophoretic isolation of cells with a particular mitochondrial structure. Based on this, we envision a label-free platform to aid the discovery process for development of therapeutics targeting the mitochondrial machinery.
[1] Kashatus, J.A., Nascimento A., Myers, L.J., Sher A., Byrne F.L., Hoehn K.L., Counter C.M., and Kashatus D.F. Erk2 Phosphorylation of Drp1 Promotes Mitochondrial Fission and MAPK-Driven Tumor Growth. Mol. Cell 57, 537–551 (2015)
See more of this Session: Electrokinetics for Cellular Analysis & Separation
See more of this Group/Topical: 2016 Annual Meeting of the AES Electrophoresis Society
See more of this Group/Topical: 2016 Annual Meeting of the AES Electrophoresis Society