Deeper Understanding of Molecular Mechanisms Underlying These Changes Could Lay the Foundation for Drug Discovery
The National Institute of General Medical Sciences, part of the National Institutes of Health (NIH), has awarded NYU College of Dentistry's Evgeny Pavlov a grant to study a phenomenon called mitochondrial permeability transition, one of the central causes of tissue damage during stroke and heart attack. The five-year, $1.9 million grant (R35GM139615) begins February 1.
Mitochondrial permeability transition is a sudden, stress-induced change to the inner membrane of the mitochondria-the cell's power generators. This process leads to energy dissipating from the mitochondria and a loss in their ability to produce energy, disrupting mitochondrial function and leading to cell death. Mitochondrial permeability transition is involved in a broad spectrum of diseases ranging from heart attack to neurodegeneration.
Pavlov, an associate professor of molecular pathobiology at NYU College of Dentistry, is working to identify and characterize the molecular mechanisms underlying mitochondrial permeability transition.
"Research shows that preventing mitochondrial permeability transition protects against cell death and tissue damage, making it an appealing target for drug treatment," said Pavlov. "However, molecular mechanisms of mitochondrial permeability transition are not well understood; this gap in knowledge prevents it from being a drug target."
Over the past five years, Pavlov's lab has demonstrated that mitochondrial permeability transition is a multifaceted phenomenon and depending on the disease type and stress severity, it can occur through different pathways. The researchers have established several original cell and animal models to study different types of mitochondrial permeability transition.
Through the new NIH-funded study, the researchers will use a variety of methods to measure mitochondrial permeability transition and tissue damage at the organism, cell, and mitochondria levels and will couple these methods with electrophysiological tests to directly measure mitochondrial permeability transition at the level of mitochondrial membranes.
Ultimately, Pavlov aims to identify the link between specific molecular mechanisms of mitochondrial permeability transition and specific stress conditions by dissecting and characterizing its multiple identities and regulation. This basic science knowledge would lay the groundwork for developing drugs that could protect against tissue damage from a stroke or heart attack.
"Our findings could illuminate one of the most critical events in cell death cascades and will bring an essential framework for the development of therapeutic approaches to target mitochondrial permeability transition," said Pavlov.
