Sub-cellular Electrophysiology
The chemical milieu within an organelle has been evolutionarily optimized to enable the biochemistry that drives organelle function. To quantitate lumenal chemistry, my lab developed a DNA-based reporter technology to derive chemical heat-maps of organelles by fluorescently imaging lumenal ions or reactive species in them (1). This technology can now be used for discovery biology or biomedical applications by interrogating organelles of cells in culture, in live multicellular organisms (2) in cells obtained from blood draws (3) or skin biopsies from human patients (4). For example we recently solved a thirty-year problem in molecular sensing by mapping lumenal calcium in acidic organelles and in doing so, identified the first example of a protein that facilitates lysosomal Ca2+ import in the animal kingdom (2). I will describe our most recent DNA-based reporter for absolute membrane potential and how we used it to end a previous misconception that many organelles, do in fact, a harbor membrane potential (4). I will close with a discussion of what it would take to develop an electrochemical model for organelle membranes, to explore the function of organelle-resident ion channels and transporters.