Elizabeth Ann Jonas

Assistant Professor
Section of Endocrinology & Metabolism

Research Interests

Our work focuses on the role of mitochondrial ion channels that regulate apoptosis and cell fate, but also act in the nervous system to control the strength of synaptic transmission. We use a set of novel techniques for the investigation of these channels, in which we record the activity of mitochondrial ion channels within intact, living neurons and within the presynaptic terminal of living neurons. We find that members of the BCL-2 family of proteins that control cell fate also regulate the strength of synaptic transmission during development, and possibly, therefore, during learning and memory. Our work further suggests that 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. Changes in mitochondrial morphology, localization and metabolism also occur in response to regulation of expression of the BCL-2 family proteins in neurons. The findings raise questions about how these properties of mitochondria help determine cell fate, synaptic fate, synaptic growth and synaptic plasticity.

Selected Publications

• Jonas, E.A., Knox, R.J. and Kaczmarek, L.K. Giga-ohm seals on intracellular membranes: A technique for studying intracellular ion channels in intact cells. Neuron 19:7-13 (1997).
• Jonas, E.A., Buchanan, J. and Kaczmarek, L.K. Prolonged activation of mitochondrial conductances during synaptic transmission. Science 286: 1347-1350 (1999).
• Jonas, E.A., Hoit, D., Hickman, J.A., Brandt, T.A., Polster, B.M., Fannjiang, Y., McCarthy, E., Montanez, M., Hardwick, J.M., Kaczmarek, L.K. Modulation of synaptic transmission by the BCL-2 family protein BCL-XL. J. Neurosci. 23: 8423-8431 (2003).
• Jonas, E.A., Hickman, J.A., Chachar, M., Polster, B.M., Brandt, T.A., Fannjiang Y., Ivanovska, I., Basanez, G., Jover, T., Kinnally, K., Zimmerberg, J., Hardwick, J.M., Kaczmarek, L.K. Pro-apoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living presynaptic terminals. Proc. Natl. Acad. Sci. USA. 101: 13590-13595 (2004).
• Jonas, E.A., Hickman, J.A., Hardwick, J.M., Kaczmarek, L.K. Exposure to hypoxia rapidly induces mitochondrial channel activity within a living synapse. J Biol Chem. 280: 4491-4497, 2005.
• Jonas, E.A., Hardwick, J.M. and Kaczmarek, L.K. Actions of BAX on mitochondrial channel activity and on synaptic transmission. Antioxidant and Redox Signaling 7: 1092-1100 (2005).
• 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. Synaptic apoptosis: The life and death of the synapse. Molecular interventions 6: 208-222 (2006).
• 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).
• 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).
• 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).
• 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).

Education:

B.A.(History), Yale University, New Haven, CT, 1982 M.D., New York University Medical School, New York, NY 1986

Contact

Campus Address
Department of Internal Medicine
Section of Endocrinology
Yale University
School of Medicine
Box 208020
New Haven, CT
06520-8020

E-mail
elizabeth.jonas@yale.edu

Telephone
203.785.5568

Fax
203.785.7670