How do proteins enter the mitochondria and cause dysregulation?

Mitochondria are critical to cellular function, producing cellular bioenergy, but they also have important roles in ion homeostasis, programmed cell death, and in ROS production and consumption. Dysregulation of any of these functions leads to mitochondrial dysfunction and human disease such as cancer, diabetes and a host of neurological disorders. Around 1500 proteins help maintain and regulate the mitochondrial and its critical functions. Of these 1500 proteins, only 13 are encoded internally while the rest are incredibly encoded in the nucleus, directed to the mitochondria, and shuttled though its complex pore through a largely undescribed process. Leveraging our recent mitochondrial import findings and our established endogenous protein tagging and in vivo tracking technology, this project aims to decipher this import process using protein tagging and proteomics, and help identify new potential drug targets.