The Waterloo Institute for Nanotechnology (WIN) is pleased to present a WIN Seminar talk by Professor Evgeny Pavlov from the Department of Molecular Pathobiology at the New York University. This seminar will be held in-person in QNC 1501 at 10am on June 24th, 2022.
Stress-Induced Mitochondrial Uncoupling (SIMU): many ways for the mitochondrion to die
Mitochondria are “power plants” that provide cells with energy in the form of ATP. ATP generation by mitochondria first requires the generation of a membrane electrochemical gradient on the mitochondrial inner membrane by the respiratory chain. The energy of this gradient is the driving force used for ATP production by the ATP synthase enzyme. This mechanism of ATP production – oxidative phosphorylation (OXPHOS) - is the process that supplies the bulk of energy to virtually all organs, including the brain and heart. Remarkably, 98% of the oxygen consumed by the human body is dedicated to OXPHOS.
Deprivation of oxygen, even for several minutes, leads to ATP depletion and death, underscoring the vital importance of OXPHOS for physiological functions. One of the essential conditions of the proper OXPHOS function is the requirement that inner membrane permeability remains low. This allows for most of the energy stored in the electrochemical gradient to be used to drive protons back inside mitochondria through ATP synthase in a process coupled to phosphorylation of ADP generating ATP.
Under normal conditions, the mitochondrial inner membrane is permeable almost exclusively to protons. However, in a broad range of pathologies, loss of mitochondrial function and cell death is linked to the loss of mitochondrial membrane potential (and ATP generation capacity) due to the increase in membrane permeability in a process that can be described as Stress-Induced Mitochondrial Uncoupling (SIMU). In my talk, I will discuss our recent experimental data that allow us to gain insight into molecular mechanisms underlying SIMU. I will also discuss the translational implications of our findings in the development of protective strategies against acute ischemic brain injury.
I obtained my PhD in Biological Physics from the Russian Academy of Sciences in 1999. After completion of the postdoctoral training at NYU Dentistry (2000-2001) and University of Calgary (2001-2005), I worked as a Research Assistant Professor at the University of Calgary and starting from 2010 as a tenure-track Assistant Professor at the Medical School at Dalhousie University, Halifax, Canada. I joined NYU Dentistry in June 2014 as a tenure track Assistant Professor and became Associate Professor in 2018.
The main focus of research in my lab is on mitochondria. In the lab, we use several experimental approaches, including imaging, electrophysiology and respirometry. We are interested in understanding the roles played by mitochondria in cell death. In particular, we are interested in understanding molecular mechanisms responsible for mitochondrial damage during stress, resulting in loss of energy homeostasis and cell damage. Our specific areas of study include mitochondrial ion channels and inorganic polyphosphate (polyP) metabolism.