The research program of the McDonald Lab focuses on how organisms transduce energy in order to thrive under challenging environmental conditions. All living things require energy to function, but the various ways that organisms do this are poorly understood. In most organisms, including people, the electron transport system (ETS) in the mitochondrion tranduces energy in the form of ATP. ATP is the energetic currency of the cell and allows organisms to grow, reproduce, and survive.
The ETS of humans is not very complicated, but most other organisms contain additional points of entry and/or exit for electrons in the ETS. Alternative oxidase (AOX) is a protein in the respiratory ETS that allows another way for electrons to exit the system. This pathway was first discovered in plants, but is present in bacteria, protists, fungi, and animals. AOX is upregulated under a variety of stressful conditions (e.g. cold temperature, disease, nutrient limitation, etc.) and our lab is working on understanding its function and regulation. Our overall research goal is to investigate the role of AOX in the acclimation of various organisms to environmental stress. We believe that AOX allows many organisms to survive environmental stress by permitting them to be flexible in the way that they transduce energy and by reducing cellular damage due to reactive oxygen species.
Research in the laboratory focuses on the role of AOX in stress tolerance in animals. We are also looking to improve the treatment of bacterial, fungal, and protistan diseases in humans by using AOX as a drug target. Finally, we are exploring the potential for using AOX in the development of new treatments for neurological (e.g. ALS, Huntington’s, Parkinson’s, dementia) and mitochondrial diseases in humans.