Grant: Project Grant

Mitochondria are the powerhouses of the cell, acting as factories that produce energy and sustain cellular metabolism. Given their central role, mitochondrial function is crucial for organismal health. Indeed, when mitochondria become dysfunctional, they can contribute to a range of diseases, including neurodegenerative disorders such as Parkinson's and Alzheimer's. To counteract mitochondrial damage, cells activate protective programs that detect and restore mitochondrial function. A common consequence of mitochondrial dysfunction is the improper delivery of proteins that are meant to enter these organelles. When proteins accumulate outside mitochondria, they act as distress signals, alerting the cell to potential damage. Understanding how these proteins function as messengers may provide new opportunities to enhance the cell's protective responses and improve resilience against disease. Our research has recently identified a novel protective program that promotes mitochondrial recovery. We discovered that a small, unique region of a mitochondrial protein plays a key role in activating this program. Under normal conditions, this region facilitates the transport of the protein into mitochondria. However, when blocked from entering the mitochondria, it adopts a different function-signaling mitochondrial stress. Our goal is to further investigate how this region enables communication between mitochondria and the rest of the cell to trigger protective responses. By uncovering fundamental mechanisms that detect and respond to mitochondrial dysfunction, our work has the potential to inform the development of therapeutic strategies aimed at enhancing cellular resilience. These insights may contribute to new approaches for treating neurodegenerative and other diseases associated with mitochondrial impairment.