Jonathan P. Hosler, PhD
I have 30 years of research experience in the area of mitochondrial bioenergetics, also known as mitochondrial physiology. I received my PhD at the University of Michigan studying electron transfer and ATP synthesis reactions associated with photosystem I of chloroplasts. I then switched to the study of mitochondria and trained with Prof. Shelagh Ferguson-Miller at Michigan State University. We developed one of the first models of Complex IV amenable to site-directed mutagenesis. At UMMC, I have worked on the role of subunit III of the catalytic core of Complex IV, on the structures that Complex IV uses to collect and introduce protons into long-range proton transfer pathways and on the assembly of copper centers in terminal oxidases. My research has been supported by the American Heart Association, NIHGMS, and the Department of Energy.
Several years ago, I began to receive requests from UMMC researchers for assistance in measuring mitochondrial function in a wide variety of experimental systems. I responded by expanding my laboratory’s capabilities and expertise to provide quantitative measurements of mitochondrial function using isolated mitochondria as well as whole cells. Our current instrumentation includes two Oroboros Oxygraph high-resolution respirometers, which are O2 electrode devices specifically engineered to provide accurate rates of O2 consumption from a minimum of biological material. One Oxygraph is further equipped with a built-in fluorimeter that allows us to measure membrane potential or H2O2 production at the same time that we measure O2 consumption. The laboratory also includes two dual-beam UV-Vis spectrophotometers and a plate reader for enzyme assays, plus a new Clarity UV-Vis spectrophotometer from OLIS. The diffuse-reflectance sample chamber of the Clarity instrument eliminates scatter from suspended particles, allowing us to obtain accurate spectra from samples containing mitochondrial membranes or whole cells. Since 2012, I have collaborated with nine local PIs on questions of mitochondrial function. Thus far, seven of these collaborations have yielded publications.
My laboratory is currently involved in elucidating the roles of natural and synthetic cyclolipopeptides (CLPs) on mitochondrial function. CLPs insert into lipid bilayers, allowing their small, cyclic peptide head groups to interact with protein near the membrane surface. We have discovered that two CLPs used as antifungal drugs in humans, micafungin and caspofungin, have novel effects on the activities of electron transfer complexes of isolated mitochondria. Micafungin also stimulates the inner mitochondrial membrane anion channel (IMAC) to transfer both anions and cations, leading to rapid mitochondrial swelling and the release of cytochrome c.