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Mitochondrial Structural and Functional Remodeling in Proinflammatory Microglial Activation

EVENT: 
Weekly Seminar
Who Should Attend: 
Researchers

Speakers

Guest Speaker
Brian M. Polster, Ph.D.
Associate Professor
Department of Anesthesiology

Research Abstract 

Neuroinflammation is thought to contribute to pathology in most neurodegenerative disorders. Microglia, the innate immune cells of the brain, are activated to proinflammatory states in response to damage-associated molecular pathogens (DAMPs) released by injured cells. During activation, microglia undergo a bioenergetic shift from oxidative phosphorylation to glycolysis. Mitochondrial structural remodeling consistent with the possibility of fission accompanies this functional change. Drp1 is the main GTPase that promotes mitochondrial fission. We hypothesized that proinflammatory microglial activation requires mitochondrial structural and bioenergetic changes that depend on Drp1 activity. Mdivi-1, a drug characterized as a Drp1 inhibitor, suppresses proinflammatory markers of microglial activation in vitro. However, surprisingly, it does so without inhibiting mitochondrial structural or functional changes. This talk will describe new targets of mdivi-1 and identify biochemical mechanisms contributing to mitochondrial respiratory suppression during microglial activation.

Brian M. Polster, Ph.D. Figure

Publications

Bordt EA, Polster BM.
NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: a bipartisan affair?
Free Radic Biol Med. 2014 Nov;76:34-46. doi: 10.1016/j.freeradbiomed.2014.07.033. Epub 2014 Aug 1.
Clerc P, Ge SX, Hwang H, Waddell J, Roelofs BA, Karbowski M, Sesaki H, Polster BM.
Drp1 is dispensable for apoptotic cytochrome c release in primed MCF10A and fibroblast cells but affects Bcl-2 antagonist-induced respiratory changes.
Br J Pharmacol. 2014 Apr;171(8):1988-99. doi: 10.1111/bph.12515.
Bordt, E.A., Clerc, P., Roelofs, B.A., Saladino, A.J., Tretter, L., Adam-Vizi, V., Cherok, E., Khalil, A., Yadava, N., Ge, S.X., Francis, T.C., Kennedy, N.W., Picton, L.K., Kumar, T., Uppuluri, S., Miller, A.M., Itoh, K., Karbowski, M., Sesaki, H., Hill, R.B., Polster, B.M.
The Putative Drp1 Inhibitor mdivi-1 Is a Reversible Mitochondrial Complex I Inhibitor that Modulates Reactive Oxygen Species.
Dev Cell. 2017 Mar 27;40(6):583-594.e6. doi: 10.1016/j.devcel.2017.02.020.

When

Tuesday, May 2, 2017 - 12:30pm

Where

Burke Medical Research Institute
785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Billings Building – Rosedale

More Information

Research Methods