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  • Jonathan P. Hosler, PhD


    Phone: (601) 984-1861
    E-mail: jhosler@umc.edu



    • PhD, University of Michigan, 1983
    • National Science Foundation Postdoctoral Fellow, Duke University, 1983-87
    • Research Assistant/Associate Professor, Dept. of Biochemistry, Michigan State University, 1987-1994, with Prof. Shelagh Ferguson-Miller
    • Professor, 2005-present; Associate Professor, 2000-05; Assistant Professor, 1995-2000: Dept. of Biochemistry, UMMC

    Research interests

    • Mitochondrial function in obesity and heart disease
    • Mechanisms of antifungal drugs
    • Mechanisms of mitochondrial electron transfer complexes

    I have been active in bioenergetics research for more than 30 years. Until recent years, my work was largely focused on complex IV of oxidative phosphorylation, the complex that transfers electrons from cytochrome c to O2 and uses the electrical energy to pump protons across the membrane. My laboratory has researched the molecular strategies used by complex IV to collect protons from solution and deliver them to the buried active site of the enzyme. We have also studied the assembly of the metal centers of complex IV. We were the first to establish that the copper chaperone Cox11 is absolutely required for the assembly of CuB. We showed that the assembly protein Surf-1 facilitates the assembly of heme A into the heme a3-CuB center. We have recently elucidated how two additional copper chaperones, Sco and PCuAC, cooperate in the assembly of the CuA center.

    Approximately three years ago, I began expanding my laboratory's capabilities and expertise to provide quantitative measurements of mitochondrial function. Several projects are currently in progress. In work that we are preparing for publication now, we show that lipopeptides used clinically to treat invasive Candida infections are also inhibitors or stimulators of complexes I, III and IV in mammalian and Candida mitochondria. The mechanisms of these lipopeptides are novel in comparison to known effectors of oxidative phosphorylation. In work with the laboratory of Dr. John Hall, Dept. of Physiology, UMMC, we show that obesity without hypertension leads to mitochondrial dysfunction in rat kidneys, but the characteristics of mitochondrial dysfunction are distinctly different depending upon the presence or absence of satiety hormone leptin. We are collaborating with Dr. Bernadette Grayson, Dept. of Neurobiology and Anatomical Sciences, UMMC, on mitochondrial changes that occur following bariatric surgery in female rats. Bariatric surgery appears to improve long-term health over and above calorie restriction. A potential mechanism for this is a positive effect on mitochondrial function. We are exploring this hypothesis in rat brain as well as peripheral tissues, such as liver. We are about to begin work with Dr. Romain Harmancey, Dept. of Physiology, UMMC, on differences in heart mitochondrial function as a result of the presence or absence of uncoupling protein 3. My laboratory colleagues in all of this are two wonderful graduate students, Kristin Shirey and Ngoc Hoang.

    Among our instrumentation are 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 a new Clarity UV-Vis spectrophotometer from OLIS. The light-integrating 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.

    Recent publications

    • Munusamy, S., do Carmo, J.M., Hosler, J.P. and Hall, J.E. (2015) Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin. In press, DOI: 10.1152/ajprenal. 00188.2015, Amer. J. Physiol.:Renal Physiol.
    • Wikstrom, M., Sharma, V., Kaila, V.R. I., Hosler,J.P. and Hummer, G. (2015) New Perspectives on Proton Pumping in Cellular Respiration. Chemical Reviews 115 (5): 2196-2221. DOI: 10.1021/cr500448tDOI
    • Alnajjar K.S., Hosler J.P. and Prochaska L. (2014) The role of the N-Terminus of subunit III in proton uptake in cytochrome c oxidase of Rhodobacter sphaeroides. Biochemistry 53: 496-504
    • Zouein, F., Duhé, R., Arany, I., Shirey, K., Hosler, J.P., Liu, H., Iman Saad, I., Kurdi, M., and Booz, G. (2014) Loss of STAT3 in mouse embryonic fibroblasts reveals its Janus-like actions on mitochondrial function and cell viability. Cytokine 66: 7-16
    • DeCoursey T.E and Hosler J. (2013) Philosophy of voltage-gated proton channels. J. R. Soc. Interface 11: Dec 18;11(92):20130799. doi: 10.1098/rsif.2013.0799.  http://dx.doi.org/10.1098/rsif.2013.0799
    • Cleary, J.D., Stover, K.R., Farley, J., Daley, W., Kyle, P.B. and Hosler, J. (2013) Cardiac Toxicity of Azole Antifungals. Pharamcology & Pharmacy 4: 362-368
    • Johansson A. L., Carlsson, J., Högbom, M., Hosler, J.P., Gennis, R.B. and P. Brzezinski (2013) Proton uptake and pKa changes in the uncoupled Asn139Cys variant of cytochrome c oxidase. Biochemistry 52: 827-36
    • L. Varanasi, J.P. Hosler (2012) Subunit III-depleted cytochrome c oxidase provides insight into the process of proton uptake by proteins, Biochim. Biophys. Acta 1817: 545-51
    • Thompson, A.K., Gray, J., Liu, A. and Hosler, J.P. (2012) The roles of Rhodobacter sphaeroides copper chaperones PCuAC and Sco (PrrC) in the assembly of the copper centers of the aa3-type and the cbb3-type cytochrome c oxidases. Biochim. Biophys Acta 1817:955-964