Identification of Novel Regulators of Mitochondrial Protein Quality Control

Abstract: Chronic pesticide exposure has been linked to several human diseases including cancer, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, cardiovascular disease, and kidney disease. Due to the potential risks to human health, the usage of pesticides has been a controversial topic. Paraquat (PQ), a commonly used pesticide worldwide, has toxic effects due to its generation of reactive oxygen species (ROS) in mitochondria and other cellular compartments. Mitochondria are an essential organelle in eukaryotic cells responsible for energy production, and thus it is intuitive that there exists a dedicated stress response pathway to protect their function. This study focuses on the mitochondria-associated degradation (MAD) pathway, which promotes mitochondrial protein quality control through identification, retrotranslocation, ubiquitination, and degradation of damaged, dysfunctional mitochondrial proteins. We have identified two novel proteins, Y and Z, in MAD, potentially as E3 ubiquitin ligases.