Elizabeth Jonas, MD, professor of internal medicine (endocrinology) and of neuroscience at Yale School of Medicine (YSM), has received her second Javits Award from the National Institute of Neurological Disorders and Stroke. Jonas was nominated for the Javits Award in 2013 for her project on Mitochondrial Ion Channels in Hypoxic Neurons.
According to the NIH, “Dr. Jonas has made significant contributions to our understanding of the mechanisms of mitochondrial physiology and pathophysiology, including making the first recordings of mitochondrial ion channel activity in intact neurons and synapses.” Jonas’ latest research focuses on the role of neuronal metabolism and mitochondrial ion channels in cell death and synaptic plasticity in acute and chronic neurodegenerative diseases. She studies ion channels located inside cells on the membranes of mitochondria, intracellular components important for cell survival, death, and energy metabolism. She is currently investigating a novel hypothesis for how changes in mitochondrial ion channels occur during stroke and how these changes contribute to neuronal death. These studies may inform the development of new therapies to protect neurons after stroke.
“The Section of Endocrinology is very proud of Dr. Jonas’ many accomplishments as recognized by her recent Javits Neuroscience Investigator Award from the National Institute of Neurological Disorders and Stroke,” said John Wysolmerski, MD, professor of medicine (endocrinology) and chief of the Section of Endocrinology & Metabolism at YSM. “This is a high honor, and it is especially telling that Dr. Jonas has now received this award for the second time,” Wysolmerski added. “She does spectacular work examining the basic aspects of mitochondrial metabolism and how these apply to neurological disease. These same basic mechanisms are likely important to better understand how mitochondrial metabolism effects cellular functions and viability in many other tissues as well. This is an important focus of research in the endocrine section as it has many implications for diseases of systemic metabolism as well as cancer.”
Jonas’ research originally focused on the role of the mitochondrial anti-death protein Bcl-xL in alteration of mitochondrial membrane channel activity during acute brain disease. Bcl-xL inhibits cell death, but it also enhances metabolism, particularly during conditioning or memory formation. Jonas’ lab found that a channel that is regulated by Bcl-xL is housed within the ATP synthase membrane-embedded c-subunit ring. She contends that the large conductance of this c-subunit leak channel suggests that it is the main inner membrane pore constituent of the eagerly sought-after death channel known as the mitochondrial permeability transition pore (mPTP), the latter of which is active during brain and cardiac ischemia (stroke and myocardial infarction). Her laboratory has found that the stoichiometry of the ATP synthase regulates mPTP open probability since the F1 portion of the ATP synthase forms an inactivating gate of the c-subunit leak channel. Experiments performed in her lab also suggest that c-subunit ring mutagenesis alters pore conductance. Therefore, a decrease in the F1 to c-subunit ratio puts cells at risk of death by mPT during brain or heart ischemia, while in contrast protective mutations in certain amino acids at the mouth of the pore decrease its ion conductance and prevent mPT. A recent publication of Jonas’ lab also identified a death-inducing mutation1, and this exact mutation was subsequently identified by another group in patients at risk for severe myocardial infarction2.
In addition to her research, Jonas mentors undergraduate, medical, and graduate students through Yale-based fellowship programs and at the Marine Biological Laboratory (MBL) in Woods Hole, Mass. During summers at the MBL, Jonas works with exchange students from the University of Puerto Rico as well as students in the National Science Foundation’s Research Experience for Undergraduate (REU) program. Jonas is also co-director of the Levin fellowship offered to Yale medical students to work at the MBL. “I have mentored between six to 15 students each year almost every year since the early days of starting my laboratory,” Jonas said.
Said Wysolmerski: “Dr. Jonas’ commitment to mentorship is exemplified by her frequent service teaching on the medical wards and the steady stream of students and trainees that populate her lab. The wholes section says congratulations Liz, and well done!”
She is currently investigating a novel hypothesis for how changes in mitochondrial ion channels occur during stroke and how these changes contribute to neuronal death. These studies may inform the development of new therapies to protect neurons after stroke.
1. Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, et al. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proc Natl Acad Sci U S A 2014, 111(29): 10580-10585.
2. Morciano G, Pedriali G, Bonora M, Pavasini R, Mikus E, Calvi S, et al. A naturally occurring mutation in ATP synthase subunit c is associated with increased damage following hypoxia/reoxygenation in STEMI patients. Cell Rep 2021, 35(2): 108983.
Yale’s Section of Endocrinology & Metabolism works to improve the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge; applying new information to patient care; and training the next generation of physicians and scientists to become leaders in the field. To learn more about their work, visit Endocrinology & Metabolism.