BME Seminars
BME 881 Seminar: Wednesday, May 7, 2008 at 4:00 pm in Bevis 245
The mitochondrial iPLA2 is a potential target for drug development directed at controlling the permeability transition
Douglas R. Pfeiffer, PhD
Professor, Department of Molecular & Cellular Biochemistry,
Director, Mitochondrial Biology Institute, The Ohio State University
Abstract
The mitochondrial permeability transition is the committed step in necrotic cell death, is required to attain apoptotic cell death in many systems, and is thought to initiate the turnover of mitochondria that have been damaged by a variety of processes. These actions of the transition apply in heart muscle subjected to ischemia/ reperfusion injury, suggesting that pharmacological agents that influence the transition could be used to minimize the extent of permanent damage that arises. The permeability transition is caused by opening a general diffusion pore within the inner mitochondrial membrane. Despite considerable effort, the molecular identity of the pore remains uncertain and this is discouraging pharmaceutical companies from continuing their programs of drug development directed at influencing the phenomenon. It is a goal of our laboratory to develop secondary targets which are already known to strongly influence the pore, sufficiently to where they would become attractive as targets for drug development relating to the transition. The secondary targets of interest are (i) a Ca2+-independent phospholipase A2 in mitochondria, (ii) the mitochondrial Ca2+ uniporter, and (iii) proteins that undergo alterations in their state of glutathiolation when mitochondria are subjected to oxidative stress. What we know at present about the Ca2+-independent phospholipase A2 will be the subject of my presentation.
