The role of BH3-only protein BNIP3 in regulation of cell survival in the brain.

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There is a balance between cell survival and death. As humans evolved, cells have developed protective strategies to prevent physiological stress from killing cells. This could be hypoxia (low oxygen) or starvation. In the brain, this protective method is essential to maintain normal functions. How the brain prevents cell death is not completely understood. We are investigating a protein called BNIP3 that may act as a master controller for cell survival. BNIP3 is found in the nucleus of brain cells, where it could lead to cell survival. BNIP3 can also be found in an alternative shorter form promoting cell survival. We are investigating how BNIP3 is controlling the balance between cell survival and cell death, by evaluating whether nuclear, or short form of BNIP3, are expressed in brain cells under normal or physiological stresses and whether this contributes to cell survival responses. Next we will define what other proteins bind to BNIP3 and what genes are blocked by BNIP3 leading to control of cell survival. In the future, this research program will discover novel genes that will increase survival of cells under stressful environments in many different types of cells and/or tissues. This research will answer fundamental questions about how cells survive stress and will provide discoveries that lead to new understanding of how cells survive stress.