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Jared Rutter

From EverybodyWiki Bios & Wiki

Jared P. Rutter is an American scientist and Distinguished Professor of Biochemistry at the University of Utah School of Medicine. He has been an investigator of the Howard Hughes Medical Institute since 2015[1]. He is known for his contributions in the areas of novel mitochondrial biochemistry, most notably the discovery and study of the mitochondrial pyruvate carrier, an obligate heterodimer made of MPC1 and MPC2 localized in the inner membrane of mitochondria, responsible for the transport of pyruvate into the mitochondria an important step in the conversion of carbohydrates into usable energy[2], and has been implicated to play important roles in human disease, including various types of cancer[3][4], and stem cell differentiation[5].

Biography[edit]

Jared P. Rutter was born in Pleasant Grove, Utah on September 26th 1973. He obtained his B.S. from Brigham Young University majoring in molecular biology. He earned his PhD in 2001 from UT Southwestern where he worked in the lab of Steven L. McKnight. Next door to them was Xiaodong Wang's lab whose work greatly inspired Rutter. He then spent 18 months as the Sara and Frank McKnight Independent Fellow of Biochemistry before joining the faculty in the Department of Biochemistry at University of Utah in 2003. He was promoted to tenured Professor of Biochemistry in 2013. He is also the Dee Glen and Ida Smith Chair for Cancer Research, Co-Director of Diabetes and Metabolism Research Center, and is Co-Leader of the Nuclear Control of Cell Growth and Proliferation Program at the Huntsman Cancer Institute.

Rutter currently resides in Salt lake City, Utah and is an avid golfer and skier. His uncle, William J. Rutter, currently the chairman and CEO of Synergenics[6], was also a Professor at University of California, San Fransisco and a cofounder of the early biotechnology company Chiron Corporation. His son Jack Rutter started the American Indie Rock Solo project Ritt Momney[7][8].

Rutter is the scientific advisor and founder of multiple biotechnology companies such as BioEnergenix and Vettore Biosciences.

Scientific Contributions[edit]

Rutter arrived to UT Southwestern as a graduate student at the same time as his advisor Steve McKnight, who was returning from industry to academia, and thus had no established projects to work on. Rutter decided to study biological rhythms and their underlying mechanisms. He examined two proteins containing a "sensing" domain known as a PAS domain. The first was NPAS2, which Rutter helped determine was involved in regulating the body's 24-hour cycle[9]. Rutter discovered that this protein acted as a bridge between the expression of circadian cycle genes and the metabolic environment of the cell by linking itself to a heme molecule that acts as a gas sensor in the cell[10]. The second protein was an enzyme called PAS kinase. Rutter found that, upon activation, this protein blocks sugar storage and stimulates protein synthesis in cells[11].

In 2008, Rutter's lab initiated a new focus on mitochondrial biochemistry and its connection with human disease. Using a combination of bioinformatics and experimental approaches, his lab identified 32 protein families that were annotated as mitochondrial, and were broadly conserved through evolution but were not functionally characterized. In the ensuing years the Rutter lab has attempted to define these functions, using a variety of model systems and approaches, and have discovered the functions of ten protein families. This directly led to the elucidation of the genetic etiology of two inherited human diseases.

The majority of these proteins (six) have been found to play a direct role in assembly and stability of the electron transport chain complexes.  Four of these proteins, known as Sdh5-8 in yeast[12] and SDHAF1-4 in mammals[13], perform specific steps in the assembly process of succinate dehydrogenase (or Complex II). The fifth (Rcfl) is specifically involved in stabilizing the assembly of the individual complexes into massive supercomplexes, which are believed to enable more efficient electron flow and ATP production. The sixth is the acyl carrier protein (ACP), which plays a novel role in coordinating OXPHOS complex and FeS complex assembly with mitochondrial metabolic state[14][15].

One of Rutter's most impactful contributions to science was the discovery in 2012[16] of the mitochondrial pyruvate transporter (MPC). The MPC is suppressed or deleted in many cancers and in stem cells and this suppression is required for the maintenance of the stem-like proliferative phenotype and promotes tumor initiation[17][18][19].

Selected awards and honors[edit]

Selected publications[edit]

  • RUTTER, J., REICK, M., WU, L. C. & MCKNIGHT, S. L. 2001. Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science, 293, 510-4.
  • HAO, H. X., KHALIMONCHUK, O., SCHRADERS, M., DEPHOURE, N., BAYLEY, J. P., KUNST, H., DEVILEE, P., CREMERS, C. W., SCHIFFMAN, J. D., BENTZ, B. G., GYGI, S. P., WINGE, D. R., KREMER, H. & RUTTER, J. 2009. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science, 325, 1139-42.
  • BRICKER, D. K., TAYLOR, E. B., SCHELL, J. C., ORSAK, T., BOUTRON, A., CHEN, Y. C., COX, J. E., CARDON, C. M., VAN VRANKEN, J. G., DEPHOURE, N., REDIN, C., BOUDINA, S., GYGI, S. P., BRIVET, M., THUMMEL, C. S. & RUTTER, J. 2012. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science, 337, 96-100.
  • VAN VRANKEN, J. G., NOWINSKI, S. M., CLOWERS, K. J., JEONG, M. Y., OUYANG, Y., BERG, J. A., GYGI, J. P., GYGI, S. P., WINGE, D. R. & RUTTER, J. 2018. ACP Acylation Is an Acetyl-CoA-Dependent Modification Required for Electron Transport Chain Assembly. Mol Cell, 71, 567-580 e4.





References[edit]

  1. "HHMI, Jared Rutter". Unknown parameter |url-status= ignored (help)
  2. Bricker, Daniel K.; Taylor, Eric B.; Schell, John C.; Orsak, Thomas; Boutron, Audrey; Chen, Yu-Chan; Cox, James E.; Cardon, Caleb M.; Van Vranken, Jonathan G.; Dephoure, Noah; Redin, Claire (2012-07-06). "A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans". Science. 337 (6090): 96–100. doi:10.1126/science.1218099. ISSN 1095-9203. PMC 3690818. PMID 22628558.
  3. Schell, John C.; Olson, Kristofor A.; Jiang, Lei; Hawkins, Amy J.; Van Vranken, Jonathan G.; Xie, Jianxin; Egnatchik, Robert A.; Earl, Espen G.; DeBerardinis, Ralph J.; Rutter, Jared (2014-11-06). "A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth". Molecular Cell. 56 (3): 400–413. doi:10.1016/j.molcel.2014.09.026. ISSN 1097-4164. PMC 4268416. PMID 25458841.
  4. Bensard, Claire L.; Wisidagama, Dona R.; Olson, Kristofor A.; Berg, Jordan A.; Krah, Nathan M.; Schell, John C.; Nowinski, Sara M.; Fogarty, Sarah; Bott, Alex J.; Wei, Peng; Dove, Katja K. (02 04, 2020). "Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier". Cell Metabolism. 31 (2): 284–300.e7. doi:10.1016/j.cmet.2019.11.002. ISSN 1932-7420. PMC 7004878 Check |pmc= value (help). PMID 31813825. Check date values in: |date= (help)
  5. Schell, John C.; Wisidagama, Dona R.; Bensard, Claire; Zhao, Helong; Wei, Peng; Tanner, Jason; Flores, Aimee; Mohlman, Jeffrey; Sorensen, Lise K.; Earl, Christian S.; Olson, Kristofor A. (September 2017). "Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism". Nature Cell Biology. 19 (9): 1027–1036. doi:10.1038/ncb3593. ISSN 1476-4679. PMC 6137334. PMID 28812582.
  6. "Synergenics". Unknown parameter |url-status= ignored (help)
  7. "Ritt Momney". Unknown parameter |url-status= ignored (help)
  8. "Ritt Momney - Salt Lake Tribune". Unknown parameter |url-status= ignored (help)
  9. Garcia, J. A.; Zhang, D.; Estill, S. J.; Michnoff, C.; Rutter, J.; Reick, M.; Scott, K.; Diaz-Arrastia, R.; McKnight, S. L. (2000-06-23). "Impaired cued and contextual memory in NPAS2-deficient mice". Science. 288 (5474): 2226–2230. doi:10.1126/science.288.5474.2226. ISSN 0036-8075. PMID 10864874.
  10. Rutter, J.; Reick, M.; Wu, L. C.; McKnight, S. L. (2001-07-20). "Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors". Science. 293 (5529): 510–514. doi:10.1126/science.1060698. ISSN 0036-8075. PMID 11441146.
  11. Rutter, J.; Michnoff, C. H.; Harper, S. M.; Gardner, K. H.; McKnight, S. L. (2001-07-31). "PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine kinase". Proceedings of the National Academy of Sciences of the United States of America. 98 (16): 8991–8996. doi:10.1073/pnas.161284798. ISSN 0027-8424. PMC 55361. PMID 11459942.
  12. Hao, Huai-Xiang; Khalimonchuk, Oleh; Schraders, Margit; Dephoure, Noah; Bayley, Jean-Pierre; Kunst, Henricus; Devilee, Peter; Cremers, Cor W. R. J.; Schiffman, Joshua D.; Bentz, Brandon G.; Gygi, Steven P. (2009-08-28). "SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma". Science. 325 (5944): 1139–1142. doi:10.1126/science.1175689. ISSN 1095-9203. PMC 3881419. PMID 19628817.
  13. Van Vranken, Jonathan G.; Bricker, Daniel K.; Dephoure, Noah; Gygi, Steven P.; Cox, James E.; Thummel, Carl S.; Rutter, Jared (2014-08-05). "SDHAF4 promotes mitochondrial succinate dehydrogenase activity and prevents neurodegeneration". Cell Metabolism. 20 (2): 241–252. doi:10.1016/j.cmet.2014.05.012. ISSN 1932-7420. PMC 4126880. PMID 24954416.
  14. Van Vranken, Jonathan G.; Nowinski, Sara M.; Clowers, Katie J.; Jeong, Mi-Young; Ouyang, Yeyun; Berg, Jordan A.; Gygi, Jeremy P.; Gygi, Steven P.; Winge, Dennis R.; Rutter, Jared (08 16, 2018). "ACP Acylation Is an Acetyl-CoA-Dependent Modification Required for Electron Transport Chain Assembly". Molecular Cell. 71 (4): 567–580.e4. doi:10.1016/j.molcel.2018.06.039. ISSN 1097-4164. PMC 6104058. PMID 30118679. Check date values in: |date= (help)
  15. Van Vranken, Jonathan G.; Jeong, Mi-Young; Wei, Peng; Chen, Yu-Chan; Gygi, Steven P.; Winge, Dennis R.; Rutter, Jared (08 19, 2016). "The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis". eLife. 5. doi:10.7554/eLife.17828. ISSN 2050-084X. PMC 4991935. PMID 27540631. Check date values in: |date= (help)
  16. Bricker, Daniel K.; Taylor, Eric B.; Schell, John C.; Orsak, Thomas; Boutron, Audrey; Chen, Yu-Chan; Cox, James E.; Cardon, Caleb M.; Van Vranken, Jonathan G.; Dephoure, Noah; Redin, Claire (2012-07-06). "A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans". Science. 337 (6090): 96–100. doi:10.1126/science.1218099. ISSN 1095-9203. PMC 3690818. PMID 22628558.
  17. Schell, John C.; Olson, Kristofor A.; Jiang, Lei; Hawkins, Amy J.; Van Vranken, Jonathan G.; Xie, Jianxin; Egnatchik, Robert A.; Earl, Espen G.; DeBerardinis, Ralph J.; Rutter, Jared (2014-11-06). "A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth". Molecular Cell. 56 (3): 400–413. doi:10.1016/j.molcel.2014.09.026. ISSN 1097-4164. PMC 4268416. PMID 25458841.
  18. Schell, John C.; Wisidagama, Dona R.; Bensard, Claire; Zhao, Helong; Wei, Peng; Tanner, Jason; Flores, Aimee; Mohlman, Jeffrey; Sorensen, Lise K.; Earl, Christian S.; Olson, Kristofor A. (September 2017). "Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism". Nature Cell Biology. 19 (9): 1027–1036. doi:10.1038/ncb3593. ISSN 1476-4679. PMC 6137334. PMID 28812582.
  19. Bensard, Claire L.; Wisidagama, Dona R.; Olson, Kristofor A.; Berg, Jordan A.; Krah, Nathan M.; Schell, John C.; Nowinski, Sara M.; Fogarty, Sarah; Bott, Alex J.; Wei, Peng; Dove, Katja K. (02 04, 2020). "Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier". Cell Metabolism. 31 (2): 284–300.e7. doi:10.1016/j.cmet.2019.11.002. ISSN 1932-7420. PMC 7004878 Check |pmc= value (help). PMID 31813825. Check date values in: |date= (help)
  20. "Sara and Frank McKnight Fellowships". Unknown parameter |url-status= ignored (help)
  21. "Science - PAS Domains and Metabolic Status Signaling" (PDF). Unknown parameter |url-status= ignored (help)
  22. "Amersham Biosciences & Science Prize for Young Scientists; Grand Prize 2003". Unknown parameter |url-status= ignored (help)
  23. "Searle Scholars - Jared Rutter, 2004". Unknown parameter |url-status= ignored (help)
  24. "Blavatnik Awards for Young Scientists National Finalists". Unknown parameter |url-status= ignored (help)
  25. "ASBMB Plenary Lecture 2015". Unknown parameter |url-status= ignored (help)


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