Elizabeth A Jonas MD

Associate Professor of Medicine (Endocrinology) and of Neurobiology

Research Interests

Mitochondrial ion channel; Regulation of apoptosis; Control of the strength of synaptic transmission in the nervous system

Current Projects

  • Role of Bcl-xL in brain ischemia
  • Role of Bcl-xL in synaptic plasticity
  • Role of Bcl-xL in neuronal metabolism
  • Role of mitochondrial bioenergetics in Parkinson's Disease

Research Summary

Some of the features of neuronal synaptic transmission that can be modified over the short and long term include changes in presynaptic calcium levels, changes in vesicle numbers and probability of release, and alterations in postsynaptic receptor numbers and function. Such variations account in part for the synaptic plasticity that may underlie learning and memory. Alterations in levels of activity at the synapse require increased energy, and therefore mitochondria could influence synaptic events by regulating the production or release of ATP, or by buffering and re-releasing calcium during vesicle fusion and recycling. BCL-2 family proteins, by their actions at mitochondrial membranes, normally play an important role in cell death at the soma, but can also strengthen or weaken synaptic connections.

Thus the actions of mitochondria at synaptic sites position these organelles to influence physiological and pathological changes in the brain. In neurodegenerative diseases, proteins that control mitochondrial ion channel activity may be key in deciding whether a synapse will live or die, and eventually, after the loss of many synaptic connections, whether a neuron will survive or undergo untimely death.


Selected Publications

  • Miyawaki, T, Mashiko, T, Ofengeim, D, Flannery RJ, Noh K-M, Fujisawa, S, Bonanni, L., Bennett, MVL, Zukin R.S, Jonas, EA. Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons. Proc. Natl. Acad. Sci. USA. 105(12):4892-7 (2008).
  • Hickman, J.A., Hardwick, J. M., Kaczmarek, L.K. and Jonas, E.A. Bcl-xL inhibitor ABT-737 reveals a dual role for Bcl-xL in synaptic transmission. J. Neurophysiol., 99, 1515-1522 (2008).
  • Li, H, Jones, A, Chen, Y, Sanger, R, Collis, L., Flannery, R., McNay, E.C., Yu, T., Schwarzenbacher, R., Bossy, B., Bossy-Wetzel, E., Bennett, M.V.L., Pypaert, M., Hickman, J.A., Smith, P. J., Hardwick, JM and Jonas, E.A. The anti-apoptotic protein BCL-xL drives synaptogenesis in cultured hippocampal neurons Proc. Natl. Acad. Sci. USA 105, 2169-2174 (2008).
  • Zhang, Y., Helm, J.S., Kaczmarek L. K. and Jonas, E.A. PKC-induced intracellular trafficking of CaV2.1 precedes its rapid recruitment to the plasma membrane. J. Neurosci. 28, 2601-2612, (2008).
  • Bonanni, L., Chachar, M., Li, H., Jones, A., Jover, T., Yakota, N., Ofengeim, D., Flannery, R.J., Miyawaki, T., Cho, C.H., Polster, B.M., Hardwick, J.M., Sensi, S., Zukin, R.S. and Jonas, E.A. Zinc-dependent multiconductance channel activity in mitochondria isolated from ischemic brain. J. Neurosci. 26: 6851-6862 (2006).
  • Jonas, E.A. (2006). Synaptic apoptosis: The life and death of the synapse. Molecular Interventions 6:208-222.

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