Skip to content

Jared Rutter

Distinguished Professor of Biochemistry and Adjunct Professor of Nutrition and Integrative Physiology

HHMI Investigator

Cancer Metabolism, Diabetes & Obesity, Metabolic Signaling

Rutter Photo

 

Molecular Biology Program

Biological Chemistry Program

Education

B.S. Brigham Young University

Ph.D. University of Texas Southwestern Medical Center

 

Research

The Rutter laboratory is interested in discovering new ways to understand metabolism and how it impacts biology and human disease. We use a variety of model systems (yeast, Drosophila, mammalian cell culture, and mice) and experimental approaches (mass spectrometry, metabolomics, next-generation sequencing, and computational) to explore these questions.

Currently, we are focused on three central areas:

MIDAS

Small molecules can modify the function of proteins; however, this allosteric regulation has historically been difficult to detect. We developed an experimental platform called MIDAS–Mass spectrometry Integrated with equilibrium Dialysis for the discovery of Allostery Systematically–that allows us to identify metabolite-protein interactions. So far, we have screened over 200 proteins, and have uncovered many new and exciting discoveries that we are now verifying using in vitro and cell culture techniques.

Mitochondrial Biology

Mitochondria are small but complex organelles with a disproportionately large impact on human health and disease. We employ a multidisciplinary approach including yeast genetics, mammalian CRISPR screens, high resolution microscopy, as well as basic biochemistry to better understand the fundamental aspects of mitochondrial biology. To date, this has revealed the function of a number of evolutionarily conserved but previously uncharacterized mitochondrial proteins, and, more recently, has provided new insights into treatments for cancer and inherited peroxisomal diseases.

Mitochondrial Pyruvate Carrier (MPC)

In 2012, we discovered a protein complex, called the Mitochondrial Pyruvate Carrier (MPC), which is the major mitochondrial pyruvate transporter in yeast, Drosophila, and humans. The fate of pyruvate–the end-product of glycolysis–is one of the most important metabolic decisions made by eukaryotic cells. In normal, differentiated mammalian cells, pyruvate is primarily transported into mitochondria where it is oxidized to produce ATP. However, in stem cells, cancer cells, and in failing hearts, pyruvate is partitioned differently, such that manipulating the MPC can impact the function and proliferation of these cell types. This supports the idea that metabolism is not just a by-product but rather a driving force governing cell fate.

 

To talk about rotation opportunities, email Jared at rutter@biochem.utah.edu

For more information, visit our website (http://rutter.biochem.utah.edu/) and follow us on Twitter @RutterLab.

References

  1. Cluntun AA, Badolia R, Lettlova S, Parnell KM, Shankar TS, Diakos NA, Olson KA, Taleb I, Tatum SM, Berg JA, Cunningham CN, Van Ry T, Bott AJ, Krokidi AT, Fogarty S, Skedros S, Swiatek WI, Yu X, Luo B, Merx S, Navankasattusas S, Cox JE, Ducker GS, Holland WL, McKellar SH, Rutter J, Drakos SG. The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure. Cell Metab. 2021 Mar 2;33(3):629-648.e10. doi: 10.1016/j.cmet.2020.12.003. Epub 2020 Dec 16. PMID: 33333007
  2. 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. Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria. Elife. 2020 Aug 17;9:e58041. doi: 10.7554/eLife.58041. PMID: 32804083
  3. Cunningham CN, Rutter J. 20,000 picometers under the OMM: diving into the vastness of mitochondrial metabolite transport. EMBO Rep. 2020 May 6;21(5):e50071. doi: 10.15252/embr.202050071. Epub 2020 Apr 23. PMID: 32329174
  4. Waller TC, Berg JA, Lex A, Chapman BE, Rutter J. Compartment and hub definitions tune metabolic networks for metabolomic interpretations. Gigascience. 2020 Jan 1;9(1):giz137. doi: 10.1093/gigascience/giz137. PMID: 31972021
  5. Berg JA, Belyeu JR, Morgan JT, Ouyang Y, Bott AJ, Quinlan AR, Gertz J, Rutter J. XPRESSyourself: Enhancing, standardizing, and automating ribosome profiling computational analyses yields improved insight into data. PLoS Comput Biol. 2020 Jan 31;16(1):e1007625. doi: 10.1371/journal.pcbi.1007625.
  6. Bensard CL, Wisidigama DR, Olson KA, Berg JA, Krah NM, Schell JC, Nowinski SM, Fogarty S, Bott AJ, Wei P, Dove KK, Tanner JM, Panic V, Cluntun A, Lettlova S, Earl CS, Namnath DF, Vázquez-Arreguín K, Villanueva CJ, Tantin D, Murtaugh LC, Evason KJ, Ducker GS, Thummel CS, Rutter J. Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier. Cell Metab. 2019 Dec 2. pii: S1550-4131(19)30609-6.  doi: 10.1016/j.cmet.2019.11.002. [Epub ahead of print]. PMID: 31813825 
  7. Kikani CK, Wu X, Fogarty S, Kang SAW, Dephoure N, Gygi SP, Sabatini DM, Rutter J. Activation of PASK by mTORC1 is required for the onset of the terminaldifferentiation program. Proc Natl Acad Sci U S A. 2019 May21;116(21):10382-10391. doi: 10.1073/pnas.1804013116. Epub 2019 May 9. PubMed PMID: 31072927; PubMed Central PMCID: PMC6534978.
  8. Nowinski SM, Van Vranken JG, Dove KK, Rutter J. Impact of Mitochondrial Fatty Acid Synthesis on Mitochondrial Biogenesis. Curr Biol. 2018 Oct
    22;28(20):R1212-R1219. doi: 10.1016/j.cub.2018.08.022. Review. PubMed PMID: 30352195; PubMed Central PMCID: PMC6258005.
  9. Van Vranken JG, Nowinski SM, Clowers KJ, Jeong MY, Ouyang Y, Berg JA, Gygi JP,Gygi SP, Winge DR, Rutter J. ACP Acylation Is an Acetyl-CoA-DependentModification Required for Electron Transport Chain Assembly. Mol Cell. 2018 Aug16;71(4):567-580.e4. doi: 10.1016/j.molcel.2018.06.039. PubMed PMID: 30118679; PubMed Central PMCID: PMC6104058.
  10. Sips PY, Shi X, Musso G, Nath AK, Zhao Y, Nielson J, Morningstar J, Kelly AE, Mikell B, Buys E, Bebarta V, Rutter J, Davisson VJ, Mahon S, Brenner M, Boss GR, Peterson RT, Gerszten RE, MacRae CA. Identification of specific metabolicpathways as druggable targets regulating the sensitivity to cyanide poisoning.PLoS One. 2018 Jun 7;13(6):e0193889. doi: 10.1371/journal.pone.0193889.eCollection 2018. PubMed PMID: 29879736; PubMed Central PMCID: PMC5991913.
  11. Zurita Rendón O, Fredrickson EK, Howard CJ, Van Vranken J, Fogarty S, TolleyND, Kalia R, Osuna BA, Shen PS, Hill CP, Frost A, Rutter J. Vms1p is a releasefactor for the ribosome-associated quality control complex. Nat Commun. 2018 Jun 6;9(1):2197. doi: 10.1038/s41467-018-04564-3. PubMed PMID: 29875445; PubMed Central PMCID: PMC5989216.
  12. Nielson JR, Rutter JP. Lipid-mediated signals that regulate mitochondrialbiology. J Biol Chem. 2018 May 18;293(20):7517-7521. doi: 10.1074/jbc.R117.001655. Epub 2018 Jan 18. Review. PubMed PMID: 29348169; PubMed  Central PMCID: PMC5961036.
  13. Nielson JR, Fredrickson EK, Waller TC, Rendón OZ, Schubert HL, Lin Z, Hill CP, Rutter J. Sterol Oxidation Mediates Stress-Responsive Vms1 Translocation to Mitochondria. Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022. PubMed PMID: 29149595; PubMed Central PMCID: PMC5837041.
  14. Schell JC, Wisidagama DR, Bensard C, Zhao H, Wei P, Tanner J, Flores A, Mohlman J, Sorensen LK, Earl CS, Olson KA, Miao R, Waller TC, Delker D, Kanth P, Jiang L, DeBerardinis RJ, Bronner MP, Li DY, Cox JE, Christofk HR, Lowry WE, Thummel CS, Rutter J. Control of intestinal stem cell function and proliferation  by mitochondrial pyruvate metabolism. Nat Cell Biol. 2017 Sep;19(9):1027-1036. doi: 10.1038/ncb3593. Epub 2017 Aug 14. PubMed PMID: 28812582; PubMed Central PMCID: PMC6137334.
  15. Diakos NA, Navankasattusas S, Abel ED, Rutter J, McCreath L, Ferrin P,McKellar SH, Miller DV, Park SY, Richardson RS, Deberardinis R, Cox JE, Kfoury AG, Selzman CH, Stehlik J, Fang JC, Li DY, Drakos SG. Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation Mismatch During Mechanical Unloading of the Failing Human Heart: Implications for Cardiac Reloading and Conditioning. JACC Basic Transl Sci. 2016 Oct;1(6):432-444. doi: 10.1016/j.jacbts.2016.06.009. Epub 2016 Oct 31. PubMed PMID: 28497127; PubMed Central PMCID: PMC5422992.
  16. Kikani CK, Wu X, Paul L, Sabic H, Shen Z, Shakya A, Keefe A, Villanueva C, Kardon G, Graves B, Tantin D, Rutter J. Pask integrates hormonal signaling with histone modification via Wdr5 phosphorylation to drive myogenesis. Elife. 2016 Sep 23;5. pii: e17985. doi: 10.7554/eLife.17985. PubMed PMID: 27661449; PubMed Central PMCID: PMC5035144.
  17. Van Vranken JG, Jeong MY, Wei P, Chen YC, Gygi SP, Winge DR, Rutter J. The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. Elife. 2016 Aug 19;5. pii: e17828. doi: 10.7554/eLife.17828. PubMed PMID: 27540631; PubMed Central PMCID: PMC4991935.
  18. Olson KA, Schell JC, Rutter J. Pyruvate and Metabolic Flexibility: Illuminating a Path Toward Selective Cancer Therapies. Trends Biochem Sci. 2016 Mar;41(3):219-230. doi: 10.1016/j.tibs.2016.01.002. Epub 2016 Feb 10. Review. PubMed PMID: 26873641; PubMed Central PMCID: PMC4783264.
  19. Schell JC, Olson KA, Jiang L, Hawkins AJ, Van Vranken JG, Xie J, Egnatchik RA, Earl EG, DeBerardinis RJ, Rutter J. A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell. 2014 Nov 6;56(3):400-13. doi: 10.1016/j.molcel.2014.09.026. Epub 2014 Oct 21. PubMed PMID: 25458841; PubMed Central PMCID: PMC4268416.
  20. Wu X, Romero D, Swiatek WI, Dorweiler I, Kikani CK, Sabic H, Zweifel BS, McKearn J, Blitzer JT, Nickols GA, Rutter J. PAS kinase drives lipogenesis through SREBP-1 maturation. Cell Rep. 2014 Jul 10;8(1):242-55. doi: 10.1016/j.celrep.2014.06.006. Epub 2014 Jul 4. PubMed PMID: 25001282; PubMed Central PMCID: PMC4112965.
  21. Van Vranken JG, Bricker DK, Dephoure N, Gygi SP, Cox JE, Thummel CS, Rutter J. SDHAF4 promotes mitochondrial succinate dehydrogenase activity and prevents neurodegeneration. Cell Metab. 2014 Aug 5;20(2):241-52. doi: 10.1016/j.cmet.2014.05.012. Epub 2014 Jun 19. PubMed PMID: 24954416; PubMed Central PMCID: PMC4126880.
  22. Chen YC, Umanah GK, Dephoure N, Andrabi SA, Gygi SP, Dawson TM, Dawson VL, Rutter J. Msp1/ATAD1 maintains mitochondrial function by facilitating the degradation of mislocalized tail-anchored proteins. EMBO J. 2014 Jul 17;33(14):1548-64. doi: 10.15252/embj.201487943. Epub 2014 May 19. PubMed PMID: 24843043; PubMed Central PMCID: PMC4198051.
  23. Bricker DK, Taylor EB, Schell JC, Orsak T, Boutron A, Chen YC, Cox JE, Cardon CM, Van Vranken JG, Dephoure N, Redin C, Boudina S, Gygi SP, Brivet M, Thummel CS, Rutter J. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012 Jul 6;337(6090):96-100. doi: 10.1126/science.1218099. Epub 2012 May 24. PubMed PMID: 22628558; PubMed Central  PMCID: PMC3690818.
  24. Heo JM, Livnat-Levanon N, Taylor EB, Jones KT, Dephoure N, Ring J, Xie J, Brodsky JL, Madeo F, Gygi SP, Ashrafi K, Glickman MH, Rutter J. A
    stress-responsive system for mitochondrial protein degradation. Mol Cell. 2010 Nov 12;40(3):465-80. doi: 10.1016/j.molcel.2010.10.021. PubMed PMID: 21070972; PubMed Central PMCID: PMC2998070.
  25. Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, Devilee  P, Cremers CW, Schiffman JD, Bentz BG, Gygi SP, Winge DR, Kremer H, Rutter J. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science. 2009 Aug 28;325(5944):1139-42. doi: 10.1126/science.1175689. Epub 2009 Jul 23. PubMed PMID: 19628817; PubMed Central  PMCID: PMC3881419.
  26. Hao HX, Cardon CM, Swiatek W, Cooksey RC, Smith TL, Wilde J, Boudina S, Abel  ED, McClain DA, Rutter J. PAS kinase is required for normal cellular energy balance. Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15466-71. Epub 2007 Sep 18. PubMed PMID: 17878307; PubMed Central PMCID: PMC2000499.
Last Updated: 7/25/21