Mitochondria are ubiquitous organelles found in all eukaryotic organisms, responsible for the generation of cellular energy via the coupling of the electron transport chain with oxidative phosphorylation. Integral to this are myriad redox-active proteins and co-factors that are involved in a delicate redox homeostasis, with redox imbalance leading to deleterious cellular effects.[1] However, limitations of current biochemical methods (reviewed elsewhere[2]) mean that novel approaches are required to better understand how dysfunctional mitochondrial redox processes lead to disease states. To approach this, we are curating a novel bioelectroanalytical approach to investigate mitochondrial redox chemistry.
Electrochemical methods are firstly being used to probe biological redox processes involving electron transfer events. Molecules such as cytochrome c and coenzyme Q10 have been studied using direct current Cyclic Voltammetry and the more sensitive[3] Fourier Transformed alternating current Voltammetry to understand the mechanistic and kinetic parameters associated with their charge transfer events. Preliminary studies using Scanning Electrochemical Cell Microscopy[4] have also been used to construct electrochemical ‘maps’ of these molecules, with the goal of developing electrochemical imaging applications in the future.
As many of these proteins and enzymes are built around a core metal ion, Inductively Coupled Plasma-Mass Spectroscopy[5] is being used to quantify the metallome of mitochondria from samples with clinical significance. This is also used to inform the choice of additional biomolecules that are screened electrochemically. Finally, Single Molecule Fluorescence Microscopy[6] is being investigated to explore the influence of redox balance on mitochondrial dynamics and health.
Our novel interdisciplinary approach to biological redox chemistry will hopefully provide more concrete understanding of the links between mitochondrial redox balance and diseases. Future applications could include diagnostic imaging, screening of therapeutics, development of disease mechanisms, and more.