Understanding How Mitochondrial Dysfunction Contributes to Human Disease

The mitochondrial electron transport chain (ETC) consists of four enzyme complexes that transfer electrons from donors like NADH to oxygen, the ultimate electron acceptor. Many metabolic pathways, including glycolysis, the TCA cycle, and beta-oxidation, produce the electron donors that fuel the ETC. In turn, ETC activity impacts a variety of processes beyond energy balance, such as reactive oxygen species (ROS) production, the redox state, mitochondrial membrane potential, mitochondrial protein import, cell death, and signaling. Dysfunctional ETC is involved in diverse pathologies like cancer and neurodegeneration but in most cases it is unclear how ETC dysfunction leads to the specific symptom. We recently found that the key function of ETC in cell proliferation is aspartate synthesis. Building upon this observation, our lab aims to understand how ETC dysfunction influences cellular process and results in diverse disease pathologies of cancer and mitochondrial disorders.