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Dennis R. Winge

Dennis R. Winge, PhD

Languages spoken: English

Academic Information

Departments Primary - Internal Medicine

Divisions:

Academic Office Information

dennis.winge@hsc.utah.edu

Research Interests

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

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.

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.

Education History

Postdoctoral Fellowship Duke University
Postdoctoral Fellow
University of Geneva
Postdoctoral Fellow
Doctoral Training Duke University
PhD
Duke University
MS
Undergraduate Concordia College
BA

Selected Publications

Journal Article

  1. Nowinski SM, Solmonson A, Rusin SF, Maschek JA, Bensard CL, Fogarty S, Jeong MY, Lettlova S, Berg JA, Morgan JT, Ouyang Y, Naylor BC, Paulo JA, Funai K, Cox JE, Gygi SP, Winge DR, DeBerardinis RJ, Rutter J (2020). Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria. Elife, 9.
  2. Hughes CE, Coody TK, Jeong MY, Berg JA, Winge DR, Hughes AL (2019). Cysteine Toxicity Drives Age-Related Mitochondrial Decline by Altering Iron Homeostasis. Cell, 180(2), 296-310.e18.
  3. Chun H, Korolnek T, Lee CJ, Coyne HJ 3rd, Winge DR, Kim BE, Petris MJ (2018). An extracellular histidine-containing motif in the zinc transporter ZIP4 plays a role in zinc sensing and zinc-induced endocytosis in mammalian cells. J Biol Chem, 294(8), 2815-2826.
  4. Van Vranken JG, Nowinski SM, Clowers KJ, Jeong MY, Ouyang Y, Berg JA, Gygi JP, Gygi SP, Winge DR, Rutter J (2018). ACP Acylation Is an Acetyl-CoA-Dependent Modification Required for Electron Transport Chain Assembly. Mol Cell, 71(4), 567-580.e4.
  5. Braymer JJ, Winge DR (2018). Sulfur from Within: Cytosolic tRNA Thiouridinylation. Cell Chem Biol, 25(6), 645-647.
  6. Garca-Guerrero AE, Camacho-Villasana Y, Zamudio-Ochoa A, Winge DR, Prez-Martnez X (2018). Cbp3 and Cbp6 are dispensable for synthesis regulation of cytochrome b in yeast mitochondria. J Biol Chem, 293(15), 5585-5599.
  7. Winge DR (2018). Filling the mitochondrial copper pool. J Biol Chem, 293(6), 1897-1898.
  8. Melber A, Winge DR (2017). Steps Toward Understanding Mitochondrial Fe/S Cluster Biogenesis. Methods Enzymol, 599, 265-292.
  9. Melber A, Winge DR (2016). Inner Secrets of the Respirasome. Cell, 167(6), 1450-1452.
  10. 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. Elife, 5.
  11. 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.
  12. 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).
  13. 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.
  14. 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.
  15. Watts T, Khalimonchuk O, Wolf RZ, Turk EM, Mohr G, Winge DR (2011). Mne1 is a novel component of the mitochondrial splicing apparatus responsible for processing of a COX1 group I intron in yeast. J Biol Chem, 286(12), 10137-46.
  16. Khalimonchuk O, Bestwick M, Meunier B, Watts TC, Winge DR (2009). Formation of the redox cofactor centers during Cox1 maturation in yeast cytochrome oxidase. Mol Cell Biol, 30(4), 1004-17.

Other

  1. Freibert SA, Boniecki MT, Stmpfig C, Schulz V, Krapoth N, Winge DR, Mhlenhoff U, Stehling O, Cygler M, Lill R (2021). N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization. Nat Commun (12(1), p. 6902). England.