Fis1 Regulation of Mitochondrial Fission

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DESCRIPTION (provided by applicant): Altered division, or fission, of mitochondrial has severe consequences even death. Yet the reasons for this are unknown. It is postulated that the mitochondria have their own lifecycle that involves fission of unhealthy mitochondria to remove them. In this model the proper balance of fission is critical: either excess or impaired fission boh result in unhealthy mitochondria. This model is compelling because it explains how alterations in fission can cause or contribute to many fundamentally different diseases including recovery from heart attack and stroke, increased metabolic stress from diabetes, normal aging, and neurodegenerative diseases such as Parkinson's and Alzheimer's disease. This research is directed towards understanding how the multi-protein machinery that is responsible for mitochondrial fission is turned on and off. To understand the protein-protein interactions that govern this, biochemical and structural studies will be integrated with cell biological and genetic approaches. A better understanding of the protein machinery and how it works will identify key points of regulation that may be targeted with small molecules to inhibitor, and activate, fission. The discovery of such molecules may ultimately lead to treatments for diseases in which enhanced, or impaired, fission is central.