Role of BH3 only protien BNIP3 in regulating hypoxia stress responses.

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There is a balance between cell survival and death to maintain healthy organisms. As humans evolved, cells have developed protective strategies to prevent physiological stress from killing them. This could be during periods of low oxygen or starvation. In the brain, this protective method is essential to maintain normal functions. How the brain prevents against cell death is not completely understood. We are investigating a protein called BNIP3 that may act as a master controller for cell survival. When BNIP3 is expressed in high levels it promotes cell death. In contrast, when BNIP3 is found in the nucleus of brain cells, it leads to cell survival. BNIP3 can also be found in an alternative shorter form that promotes cell survival. We are investigating how BNIP3 is controlling the balance between cell survival and cell death through a process called autophagy. Autophagy is a process where the cell can recycle material to create nutrients and maintain cell survival. If autophagy is prolonged, it will lead to cell death. We will evaluate how the nuclear or short form of BNIP3 affect autophagy under physiological stresses. Next, we will define what other proteins bind to BNIP3 and what genes are involved leading to cell survival. This research will answer fundamental questions and provide discoveries that could lead to a new understanding of how cells survive physiological stresses.