Dr. Hilla Weidberg receives Fall 2021 CIHR project grant

Molecular mechanisms of sensing and repairing dysfunctional mitochondrial protein import

Principal Investigator: Dr. Hilla Weidberg

Abstract

Mitochondria are essential factories within cells that manufacture energy and building blocks. A critical requirement for mitochondria to function properly is the ability to deliver proteins, the “factory manufacturing workers”, into the mitochondria. Defective mitochondrial protein delivery is a feature of aged cells and many human diseases, including heart and blood vessel diseases, and neurodegenerative diseases like Parkinson’s and Alzheimer’s. As these diseases affect a growing number of people in Canada, it is extremely important and timely to broaden our knowledge of how cells maintain mitochondrial and cellular health when mitochondrial protein delivery is impaired. I recently discovered a new monitoring (surveillance) pathway, called the mitochondrial compromised protein import response (mitoCPR), which promotes mitochondrial and cell recovery when protein delivery is not efficient. This work showed that problems in the delivery process lead to incomplete entry of proteins into the mitochondria, and to clogging of the protein entry sites. We aim to gain a deeper understanding of how the mitoCPR helps unclog and recover mitochondria under physiological and disease conditions. Using molecular biology and advanced technologies such as gene editing and proteomics, we will reveal how the cell keeps mitochondria healthy. This research holds potential for treatment strategies for neurodegenerative and other diseases where mitochondrial dysfunction plays a role.