Evgeny Pavlov, PhD, assistant professor of basic science and craniofacial biology, has been awarded a three-year, $300,000 grant from the American Heart Association (AHA) to study the phenomenon called mitochondrial permeability transition. Permeability transition—a sudden increase in permeability of the mitochondrial membrane during stress— is a major cause of cell death and therefore tissue damage during stroke and heart attack.
Preventing excessive cell death is a key challenge during the treatment of stroke and heart attack. Identifying central events at the molecular level which occur during pathology and are responsible for cell death is critical in addressing this challenge.
Permeability transition is caused by the opening of the permeability transition pore, a macromolecular complex in mitochondria. The opening of the pore leads to the loss of mitochondrial function, energy collapse, and ultimately cell death.
Blocking the permeability transition pore is thought to be a highly efficient treatment strategy. Researchers have extensively studied the molecular architecture of the permeability transition pore, but the mechanism of the formation of the pore remains controversial and is the subject of many scientific debates.
Based on Dr. Pavlov's preliminary findings, he hypothesizes that the permeability transition pore can be formed with the participation of several different proteins which are activated by the same activation pathway. The central goal of the AHA-funded research is to perform electrophysiological and biochemical studies to test this hypothesis and identify the molecular pathways leading to the formation of the pore.
The prevention of permeability transition has the potential to become an effective target for drug treatment, including for drugs that could be used for protection against tissue damage from a stroke or heart attack.
"Incomplete knowledge of the molecular events leading to permeability transition activation is a major obstacle in the way of progress towards development of such drugs. Understanding the molecular mechanisms of permeability transition formation and activation will create a basic science foundation for the future development of compounds that can help to prevent permeability transition and help to develop more efficient disease treatment strategies" said Dr. Pavlov.