Join us for a special research seminar presented by Dr. Varda Shoshan-Barmatz titled, “Mitochondrial gatekeeper VDAC1 overexpression and oligomerization lies at the intersection of programmed cell death, inflammation and disease.”
Wednesday, April 3 via Zoom
9 AM Pacific, 12 noon Eastern, 5 PM UK, 7 PM Israel time
Introduced and Moderated by Amédée des Georges of New York University, formerly at City College and ASRC, CUNY’s Advanced Science Research Center.
* Dr. Varda Shoshan-Barmatz will be giving this talk online via Zoom. Please contact Amédée des Georges at ajd9478@nyu.edu for any questions.
Access Zoom info by registering here.
Or at https://tinyurl.com/Varda-S-B
Abstract Mitochondria are the signaling hub for regulating metabolism, apoptosis, cell cycle, proliferation, differentiation, epigenetics, immune signaling, and aging processes. The voltage-dependent anion channel 1 (VDAC1) serves as a mitochondrial gatekeeper, a channel that controls the flux of ions, including Ca2+, nucleotides, and metabolites across the outer mitochondrial membrane (OMM), and also as a key protein in mitochondria-mediated apoptosis. Thus, VDAC1 stands at the crossroads between mitochondrial energy production and metabolism, Ca2+ homeostasis, apoptosis, and other cell stress-associated processes. The location at the interface between the cytosol and mitochondria, positions VDAC1 to serve as a hub protein, and the interactions with over 100 proteins allow the molecule to mediate and regulate the integration of mitochondrial functions with cellular activities. Apoptotic signals cause mitochondrial membrane permeability changes, which allow the release of apoptogenic proteins. However, it remains unclear how these apoptotic initiators cross the OMM and are subsequently released into the cytosol to activate apoptosis.
Recently, we demonstrated that induction of apoptosis leads to VDAC1 overexpression and oligomerization regardless of the cell type, apoptosis inducer used, that all affect the mitochondria, yet acting via different mechanisms. Accordingly, we proposed a new concept for apoptosis induction by which apoptosis inducers, stress, or diseases state, induce VDAC1 overexpression, and thereby shift the equilibrium between monomeric and oligomeric states. This promotes the formation of a large channel within the VDAC1 homo-oligomer, which then acts as a conduit for pro-apoptotic protein release and subsequent apoptosis. Oligomeric VDAC1 is also at the nexus of mitochondrial DNA (mtDNA) release and is implicated in impairing the innate immune system because the mtDNA fragments released into the cytosol trigger type-Ι interferon signaling and inflammation. Moreover, we have demonstrated that overexpression of VDAC1 is a common threat in diabetes, and in neurodegenerative, cardiac, and autoimmune diseases. In addition, others have demonstrated associations between VDAC1 overexpression and oligomerization, and acute liver injury, rheumatoid arthritis, spinal cord injury, and COVID-19. Thus, inhibiting VDAC1 overexpression and/or oligomerization represents an effective strategy to treat these diseases. With the perception of VDAC1 as an innovative target for the control of dysregulated cell metabolism, inflammation, and programed cell death associated with various diseases, we have developed the new VDAC1-interacting molecules, VBIT-4 and VBIT-12. These molecules prevent VDAC1 oligomerization, cell death, mitochondrial dysfunction, and inflammation and abolish the mpathophysiology of various diseases as demonstrated in mouse models for type-2-diabetes, lupus, colitis, Alzheimer’s disease, acute liver injury, spinal cord minjury, and COVID-19. Our findings implicate VDAC1 as the link between mitochondrial dysfunction and a wide range of diseases, and place it at the crossroads between metabolism, cell survival, cell death, and inflammation.
Speaker info:
Dr. Varda Shoshan-Barmatz is Professor of Molecular Physiology at Ben-Gurion University in Israel and received her Ph.D. from the Weizmann Institute of Science and did post-doctoral studies at the University of Wisconsin-Madison and at the University of Toronto. She established the National Institute for Biotechnology in Israel and served as its director from 2006-2015.
This seminar has been organized by Manfred Philipp. Sponsored by CUNY’s Advanced Science Research Center, the CUNY Academy for the Humanities and Sciences, the CUNY Graduate Center’s Biochemistry Doctoral Program, the CUNY Graduate Center’s Interdisciplinary Concentration in Cognitive Science, the STEM Section of the Academic Engagement Network, and Americans for Ben-Gurion University.
Download the flyer for this seminar here: