Dennis R. Winge, Ph.D.

Research Interests

  • Hemeproteins
  • Mitochondria
  • Cell Respiration
  • Cancer Metabolism
  • Metal Metabolism
  • Copper
  • Oxidative Phosphorylation
  • Oxidative Stress
  • Paraganglioma

Languages

  • English

Academic Information

  • Departments: Biochemistry - Research Professor, Internal Medicine - Professor
  • Divisions: Hematology/BMT
  • Cancer Center Programs: Nuclear Control of Cell Growth & Differentiation

Academic Office Information

  • (801) 585-5103
  • School of Medicine
    Hematology and Hematologic Malignancies
    30 N 1900 E
    Salt Lake City, UT 84132

Research Statement

Research in the Winge laboratory is focused on cellular mitochondria. One major focus is the biogenesis of the mitochondrial electron transfer respiratory complexes II, III and IV within this organelle. Improper assembly of these complexes are evident in inherited and acquired diseases of patients with cardiomyopathy, hepatopathy, and neurological disorders. A key step in assembly of these complexes is the formation of their essential flavin, heme, and iron-sulfur centers, which are inserted by the involvement of assembly factor proteins. Much of the current knowledge on the biogenesis of theses respiratory complexes was elucidated in Saccharomyces cerevisiae, and many of the known assembly factors are conserved in in humans. We seek to identify new proteins that mediate the biogenesis of succinate dehydrogenase, cytochrome c reductase and cytochrome c oxidase complexes and elucidate their mechanism of action. We use a combination of in vitro biochemical, in vivo cellular assays and genetic analyses in these pursuits. Specifically, we are studying how flavin and three iron-sulfur centers are formed in succinate dehydrogenase, how the heme andiron-sulfur centers are formed in cytochrome c reductase and the pathway ofcopper and heme a center formation in cytochrome oxidase. In these studies we are focused on known assembly factors as well as seeking novel factors that mediate formation of the redox centers.

Academic Bio

Dennis Winge, Ph.D. is a Professor of Medicine in the Division of Hematology and Hematologic Malignancies, Department of Internal Medicine at the University of Utah School of Medicine. He is also a Research Professor of Biochemistry in the Department of Biochemistry at the University of Utah. He is Director of the Biological Chemistry PhD graduate program at the University. Research in the Winge laboratory is focused on cellular mitochondria. One major focus is the biogenesis of the mitochondrial electron transfer respiratory complexes II, III and IV within this organelle. Improper assembly of these complexes are evident in inherited and acquired diseases of patients with cardiomyopathy, hepatopathy, and neurological disorders. A key step in assembly of these complexes is the formation of their essential flavin, heme, and iron-sulfur centers, which are inserted by the involvement of assembly factor proteins. Much of the current knowledge on the biogenesis of theses respiratory complexes was elucidated in Saccharomyces cerevisiae, and many of the known assembly factors are conserved in humans. Dr. Winge and his team seek to identify new proteins that mediate the biogenesis of succinate dehydrogenase, cytochrome c reductase and cytochrome c oxidase complexes, and then elucidate their mechanism of action. They use a combination of in vitro biochemical, in vivo cellular assays and genetic analyses in these pursuits. Specifically, they study how flavin and three iron-sulfur centers are formed in succinate dehydrogenase, how the heme andiron-sulfur centers are formed in cytochrome c reductase and the pathway of copper and heme a center formation in cytochrome oxidase. In these studies, research focuses on known assembly factors, as well as seeking novel factors that mediate formation of the redox centers.Dr. Winge received his Bachelor of Arts in Chemistry (Honors) at Concordia College in Morehead, Minnesota, after which he attended Duke University, earning first his M.S. and then his Ph.D. in Biochemistry. He completed two Postdoctoral Fellowships in Biochemistry, one at the University of Geneva in Geneva, Switzerland, and one at Duke University. He joined the faculty at the University of Utah in 1979. He currently serves on the Editorial Board for the Journal of Biological Chemistry, and received status as a Fellow of the American Association for the Advancement of Science in 2010. He has served as supervisor and/or mentor for nearly 80 high school, undergraduate, graduate and doctoral students, as well as served as a member on over 50 Ph.D./Doctorate Thesis Committees for the Departments of Biochemistry, CVMB, Biology, Chemistry, Human Genetics, Oncological Sciences and Pathology. Since 1979, Dr. Winge has published nearly 220 journal articles, reviews, books and book chapters.

Education History

Type School Degree
Postdoctoral Fellowship Duke University
Biochemistry
Postdoctoral Fellow
Postdoctoral Fellowship University of Geneva
Biochemistry
Postdoctoral Fellow
Doctoral Training Duke University
Biochemistry
Ph.D.
Graduate Training Duke University
Biochemistry
M.S.
Undergraduate Concordia College
Chemistry (Honors)
B.A.

Global Impact

Education History

Type School Degree Country
Postdoctoral Fellowship University of Geneva
Biochemistry
Postdoctoral Fellow Switzerland

Career

Institution Description Country
University of Geneva, Deptartment of Biochemistry Research Associate Switzerland

Selected Publications

Journal Article

  1. The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis.LID - 10.7554/eLife.17828 [doi]LID - e17828 [pii]Van Vranken JG, Jeong MY, Wei P, Chen YC, Gygi SP, Winge DR, Rutter J (2016). The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis.LID - 10.7554/eLife.17828 [doi]LID - e17828 [pii]. Elife, 5.
  2. Inner Secrets of the Respirasome.Melber A, Winge DR (2016). Inner Secrets of the Respirasome. Cell, 167(6), 1450-1452.
  3. VanVraken JG, Jeong MY, Gygi SP, Winge D, Rutter J (2016). The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. eLife, 19(5).
  4. The Plasma Membrane Protein Nce102 Implicated in Eisosome Formation Rescues a Heme Defect in Mitochondria.Kim HJ, Jeong MY, Parnell TJ, Babst M, Phillips JD, Winge DR (2016). The Plasma Membrane Protein Nce102 Implicated in Eisosome Formation Rescues a Heme Defect in Mitochondria. J Biol Chem, 291(33), 17417-26.
  5. Protein-mediated assembly of succinate dehydrogenase and its cofactors.Van Vranken JG, Na U, Winge DR, Rutter J (2015). Protein-mediated assembly of succinate dehydrogenase and its cofactors. Crit Rev Biochem Mol Biol, 50(2), 168-80.
  6. The LYR factors SDHAF1 and SDHAF3 mediate maturation of the iron-sulfur subunit of succinate dehydrogenase.Na U, Yu W, Cox J, Bricker DK, Brockmann K, Rutter J, Thummel CS, Winge DR (2014). The LYR factors SDHAF1 and SDHAF3 mediate maturation of the iron-sulfur subunit of succinate dehydrogenase. Cell Metab, 20(2), 253-66.
  7. Dela Cruz R, Jeong MY, Winge DR (in press). Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis. Microb Cell.