Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT)—relationship to newly identified mitochondrial pyruvate carrier proteins
Open accessAbstract
Thiazolidinedione (TZD) insulin sensitizers have the potential to effectively treat a number of human diseases, however the currently available agents have dose-limiting side effects that are mediated via activation of the transcription factor PPARγ. We have recently shown PPARγ-independent actions of TZD insulin sensitizers, but the molecular target of these molecules remained to be identified. Here we use a photo-catalyzable drug analog probe and mass spectrometry-based proteomics to identify a previously uncharacterized mitochondrial complex that specifically recognizes TZDs. These studies identify two well-conserved proteins previously known as brain protein 44 (BRP44) and BRP44 Like (BRP44L), which recently have been renamed Mpc2 and Mpc1 to signify their function as a mitochondrial pyruvate carrier complex. Knockdown of Mpc1 or Mpc2 in Drosophila melanogaster or pre-incubation with UK5099, an inhibitor of pyruvate transport, blocks the crosslinking of mitochondrial membranes by the TZD probe. Knockdown of these proteins in Drosophila also led to increased hemolymph glucose and blocked drug action. In isolated brown adipose tissue (BAT) cells, MSDC-0602, a PPARγ-sparing TZD, altered the incorporation of (13)C-labeled carbon from glucose into acetyl CoA. These results identify Mpc1 and Mpc2 as components of the mitochondrial target of TZDs (mTOT) and suggest that understanding the modulation of this complex, which appears to regulate pyruvate entry into the mitochondria, may provide a viable target for insulin sensitizing pharmacology.
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The MPC is a target of thiazolidinediones and a regulator of insulin secretion.
“In fact, the MPC has emerged as an unanticipated target of thiazolidinediones (Colca et al., 2013; Divakaruni et al., 2013), a class of insulin sensitizing drugs, and as a regulator of insulin secretion (Patterson et al., 2014; Vigueira et al., 2014);”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Colca et al., 2013
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Wild, S., Roglic, G., Green, A., Sicree, R., & King, H. (2004) · Diabetes Care · doi:10.2337/diacare.27.5.1047 · Cited by 15,297 · see citing works
Interplay between lipids and branched-chain amino acids in development of insulin resistance
Newgard, C. B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.024 · Cited by 1,080 · see citing works
Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARγ by Cdk5
Choi, J. H., Banks, A. S., Estall, J. L., Kajimura, S., Boström, P., Laznik, D., Ruas, J. L., Chalmers, M. J., Kamenecka, T. M., Blüher, M., et al. (2010) · Nature · doi:10.1038/nature09291 · Cited by 886 · see citing works
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., et al. (2012) · Science · doi:10.1126/science.1218099 · Cited by 843 · see citing works
Identification and Functional Expression of the Mitochondrial Pyruvate Carrier
Herzig, S., Raemy, E., Montessuit, S., Veuthey, J.-L., Zamboni, N., Westermann, B., Kunji, E. R. S., & Martinou, J.-C. (2012) · Science · doi:10.1126/science.1218530 · Cited by 747 · see citing works
Sunny, N. E., Parks, E. J., Browning, J. D., & Burgess, S. C. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.11.004 · Cited by 672 · see citing works
A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila
Musselman, L. P., Fink, J. L., Narzinski, K., Ramachandran, P. V., Hathiramani, S. S., Cagan, R. L., & Baranski, T. (2011) · Disease Models & Mechanisms · doi:10.1242/dmm.007948 · Cited by 564 · see citing works
Kusminski, C. M., Holland, W. L., Sun, K., Park, J., Spurgin, S. B., Lin, Y., Askew, G. R., Simcox, J., McClain, D. A., Li, C., et al. (2012) · Nature Medicine · doi:10.1038/nm.2899 · Cited by 466 · see citing works
Satapati, S., Sunny, N. E., Kucejova, B., Fu, X., He, T. T., Méndez-Lucas, A., Shelton, J. M., Perales, J. C., Browning, J. D., & Burgess, S. C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m023382 · Cited by 407 · see citing works
Colca, J. R., McDonald, W. G., Waldon, D. J., Leone, J. W., Lull, J. M., Bannow, C. A., Lund, E. T., & Mathews, W. R. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00424.2003 · Cited by 339 · see citing works
Self-citationWiley, S. E., Murphy, A. N., Ross, S. A., van der Geer, P., & Dixon, J. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701078104 · Cited by 326 · see citing works
Self-citationThiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier
Divakaruni, A. S., Wiley, S. E., Rogers, G. W., Andreyev, A. Y., Petrosyan, S., Loviscach, M., Wall, E. A., Yadava, N., Heuck, A. P., Ferrick, D. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303360110 · Cited by 308 · see citing works
Self-citationMitoNEET is a uniquely folded 2Fe-2S outer mitochondrial membrane protein stabilized by pioglitazone
Paddock, M. L., Wiley, S. E., Axelrod, H. L., Cohen, A. E., Roy, M., Abresch, E. C., Capraro, D. T., Murphy, A. N., Nechushtai, R., Dixon, J. E., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707189104 · Cited by 302 · see citing works
Self-citationReceptor-independent actions of PPAR thiazolidinedione agonists: Is mitochondrial function the key?
Feinstein, D. L., Spagnolo, A., Akar, C., Weinberg, G., Murphy, P., Gavrilyuk, V., & Russo, C. D. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.03.033 · Cited by 275 · see citing works
Lorenz, M. A., Burant, C., & Kennedy, R. T. (2011) · Analytical Chemistry · doi:10.1021/ac103313x · Cited by 233 · see citing works
The Outer Mitochondrial Membrane Protein mitoNEET Contains a Novel Redox-active 2Fe-2S Cluster
Wiley, S. E., Paddock, M. L., Abresch, E. C., Gross, L. A., van der Geer, P., Nechushtai, R., Murphy, A. N., Jennings, P. A., & Dixon, J. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700107200 · Cited by 179 · see citing works
Self-citationType 2 Diabetes Can Be Prevented With Early Pharmacological Intervention
DeFronzo, R. A., & Abdul‐Ghani, M. A. (2011) · Diabetes Care · doi:10.2337/dc11-s221 · Cited by 148 · see citing works
Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist
Petrovič, N., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00035.2008 · Cited by 134 · see citing works
Chen, Z., Vigueira, P. A., Chambers, K. T., Hall, A. M., Mitra, M. S., Qi, N., McDonald, W. G., Colca, J. R., Kletzien, R. F., & Finck, B. N. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.363960 · Cited by 121 · see citing works
Self-citationPPAR gamma and the molecular control of adipogenesis
Brun, R., & Spiegelman, B. M. (1997) · Journal of Endocrinology · doi:10.1677/joe.0.1550217 · Cited by 114 · see citing works
Induction of uncoupling protein in brown adipose tissue
Foellmi, L. A., Wyse, B. M., Herron, D., Nedergaard, J., & Kletzien, R. F. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(96)00345-0 · Cited by 86 · see citing works
Self-citationClinical Proof-of-Concept Study With MSDC-0160, a Prototype mTOT-Modulating Insulin Sensitizer
Colca, J. R., VanderLugt, J. T., Adams, W. J., Shashlo, A., McDonald, W. G., Liang, J., Zhou, R., & Orloff, D. G. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2013.10 · Cited by 85 · see citing works
Self-citationRosiglitazone, PPARγ, and Type 2 Diabetes
Kahn, B. B., & McGraw, T. E. (2010) · New England Journal of Medicine · doi:10.1056/nejmcibr1012075 · Cited by 59 · see citing works
Zuris, J. A., Ali, S. S., Yeh, H., Nguyen, T. A., Nechushtai, R., Paddock, M. L., & Jennings, P. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.319731 · Cited by 43 · see citing works
The Mitochondrial Pyruvate Carrier: Has It Been Unearthed at Last?
Halestrap, A. P. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.013 · Cited by 40 · see citing works
What has prevented the expansion of insulin sensitisers?
Colca, J. R., & Kletzien, R. F. (2006) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.15.3.205 · Cited by 40 · see citing works
Self-citationColca, J. R. (2004) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207043328337 · Cited by 22 · see citing works
Self-citationRyder, R. E. J. (2011) · The British Journal of Diabetes · doi:10.1177/1474651411412658 · Cited by 20 · see citing works
Benga, G., Hodârnău, A., Tilinca, R., Poruţiu, D., Dancea, S., Pop, V. I., & Wrigglesworth, J. M. (1979) · Journal of Cell Science · doi:10.1242/jcs.35.1.417 · Cited by 20 · see citing works
High-Throughput Flow Cytometry–Based Assay to Identify Apoptosis-Inducing Proteins
Sauermann, M., Hahne, F., Schmidt, C., Majety, M., Rosenfelder, H., Bechtel, S., Huber, W. K., Poustka, A., Arlt, D., & Wiemann, S. (2007) · SLAS DISCOVERY · doi:10.1177/1087057107301271 · Cited by 6 · see citing works
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PPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
Gross, B., Pawlak, M., Lefebvre, P., & Staels, B. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.135 · Cited by 778 · see citing works
Tang, T., Lord, J. M., Norman, R. J., Yasmin, E., & Balen, A. H. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053.pub5 · Cited by 698 · see citing works
Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes
Soccio, R. E., Chen, E. R., & Lazar, M. A. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.08.005 · Cited by 518 · see citing works
Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus
Ferguson, D., & Finck, B. N. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00507-z · Cited by 507 · see citing works
Self-citationCurrent and upcoming pharmacotherapy for non-alcoholic fatty liver disease
Rotman, Y., & Sanyal, A. J. (2016) · Gut · doi:10.1136/gutjnl-2016-312431 · Cited by 410 · see citing works
Targeting hepatic glucose metabolism in the treatment of type 2 diabetes
Rines, A. K., Sharabi, K., Tavares, C. D. J., & Puigserver, P. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.151 · Cited by 380 · see citing works
Schell, J. C., Olson, K. A., Jiang, L., Hawkins, A. J., Van Vranken, J. G., Xie, J., Egnatchik, R. A., Earl, E. G., DeBerardinis, R. J., & Rutter, J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.026 · Cited by 363 · see citing works
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Smith, E. M., & Collins, I. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.14.152 · Cited by 356 · see citing works
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Meissner, F., Geddes‐McAlister, J., Mann, M., & Bantscheff, M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00409-3 · Cited by 355 · see citing works
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Athauda, D. S., & Foltynie, T. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.10.001 · Cited by 333 · see citing works
Sunny, N. E., Bril, F., & Cusi, K. J. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.11.006 · Cited by 321 · see citing works
Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier
Divakaruni, A. S., Wiley, S. E., Rogers, G. W., Andreyev, A. Y., Petrosyan, S., Loviscach, M., Wall, E. A., Yadava, N., Heuck, A. P., Ferrick, D. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303360110 · Cited by 308 · see citing works
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Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier
Vacanti, N. M., Divakaruni, A. S., Green, C. R., Parker, S. J., Henry, R. R., Ciaraldi, T. P., Murphy, A. N., & Metallo, C. M. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.024 · Cited by 277 · see citing works
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Wang, H., Mehal, W. Z., Nagy, L. E., & Rotman, Y. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00579-3 · Cited by 222 · see citing works
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Self-citationHarrison, S. A., Alkhouri, N., Davison, B. A., Sanyal, A., Edwards, C., Colca, J. R., Lee, B. H., Loomba, R., Cusi, K., Kolterman, O., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.10.023 · Cited by 211 · see citing works
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McGown, C., Birerdinc, A., & Younossi, Z. M. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2013.09.012 · Cited by 194 · see citing works
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Skat‐Rørdam, J., Ipsen, D. H., Lykkesfeldt, J., & Tveden‐Nyborg, P. (2018) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13190 · Cited by 194 · see citing works
Ghosh, A., Tyson, T., George, S., Hildebrandt, E. N., Steiner, J. A., Madaj, Z., Schulz, E., Machiela, E., McDonald, W. G., Galvis, M. L. E., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aag2210 · Cited by 187 · see citing works
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Gao, R., Li, Y., Xu, Z., Zhang, F., Xu, J., Hu, Y., Yin, J., Yang, K., Sun, L., Wang, Q., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000279 · Cited by 179 · see citing works
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Yin, Y., Choi, S., Xu, Z., Zeumer, L., Kanda, N., Croker, B. P., & Morel, L. M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501537 · Cited by 170 · see citing works
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McCommis, K. S., Hodges, W. T., Brunt, E. M., Nalbantoglu, I., McDonald, W. G., Holley, C. L., Fujiwara, H., Schaffer, J. E., Colca, J. R., & Finck, B. N. (2016) · Hepatology · doi:10.1002/hep.29025 · Cited by 138 · see citing works
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Lee, M. A., Tan, L., Yang, H., Im, Y.-G., & Im, Y. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-17082-x · Cited by 108 · see citing works
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Vallée, A., Lecarpentier, Y., Guillevin, R., & Vallée, J.-N. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00352 · Cited by 66 · see citing works
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Yiew, N. K. H., & Finck, B. N. (2022) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00074.2022 · Cited by 63 · see citing works
Self-citationVanderperre, B., Herzig, S., Krznar, P., Hörl, M., Ammar, Z., Montessuit, S., Pierredon, S., Zamboni, N., & Martinou, J. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006056 · Cited by 63 · see citing works
Colca, J. R., Tanis, S. P., McDonald, W. G., & Kletzien, R. F. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2013.839659 · Cited by 61 · see citing works
Self-citationMorris, O., Deng, H., Tam, C., & Jasper, H. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108423 · Cited by 58 · see citing works
Mitochondrial pyruvate carrier function and cancer metabolism
Rauckhorst, A. J., & Taylor, E. B. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.05.003 · Cited by 58 · see citing works
Shah, R. C., Matthews, D. C., Andrews, R. D., Capuano, A. W., Fleischman, D. A., VanderLugt, J. T., & Colca, J. R. (2014) · Current Alzheimer Research · doi:10.2174/1567205011666140616113406 · Cited by 57 · see citing works
Self-citationWang, Q. A., Zhang, F., Jiang, L., Ye, R., An, Y., Shao, M., Tao, C., Gupta, R. K., & Scherer, P. E. (2018) · Molecular and Cellular Biology · doi:10.1128/mcb.00677-17 · Cited by 54 · see citing works
Brust, R., Lin, H., Fuhrmann, J., Asteian, A., Kamenecka, T. M., & Kojetin, D. J. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.6b01015 · Cited by 53 · see citing works
Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter
Nagampalli, R. S. K., Quesñay, J. E. N., Adamóski, D., Islam, Z., Birch, J., Sebinelli, H. G., Girard, R. M. B. M., Ascenção, C. F. R., Fala, A. M., Pauletti, B. A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-21740-z · Cited by 53 · see citing works
Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease
Steensels, S., Qiao, J., & Ersoy, B. A. (2020) · Metabolites · doi:10.3390/metabo10070283 · Cited by 51 · see citing works
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Mocholí, E., Russo, L., Gopal, K., Ramstead, A. G., Hochrein, S. M., Vos, H. R., Geeven, G., Adegoke, A., Hoekstra, A. T., van Es, R. M., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112583 · Cited by 44 · see citing works
Foltynie, T., & Athauda, D. S. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.008 · Cited by 44 · see citing works
Tavoulari, S., Sichrovsky, M., & Kunji, E. R. S. (2023) · Acta Physiologica · doi:10.1111/apha.14016 · Cited by 43 · see citing works
Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes
Matsumoto, Y., Ishii, M., Hayashi, Y., Miyazaki, S., Sugita, T., Sumiya, E., & Sekimizu, K. (2015) · Scientific Reports · doi:10.1038/srep10722 · Cited by 42 · see citing works
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Colca, J. R., & Scherer, P. E. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101409 · Cited by 37 · see citing works
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Hodges, W. T., Jarasvaraparn, C., Ferguson, D., Griffett, K., Gill, L. E., Chen, Y., Ilagan, M. X. G., Hegazy, L., Elgendy, B., Cho, K., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101554 · Cited by 36 · see citing works
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Tavoulari, S., Schirris, T. J. J., Mavridou, V., Thangaratnarajah, C., King, M. S., Jones, D. T. D., Ding, S., Fearnley, I. M., & Kunji, E. R. S. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101469 · Cited by 38 · see citing works
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Self-citationTulloch, L. B., Menzies, S. K., Fraser, A. L., Gould, E., King, E. F. B., Zacharova, M. K., Florence, G. J., & Smith, T. (2017) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0005886 · Cited by 35 · see citing works
Beňová, A., Ferenčáková, M., Bardová, K., Funda, J., Procházka, J., Špoutil, F., Čajka, T., Dzubanova, M., Balcaen, T., Kerckhofs, G., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101598 · Cited by 34 · see citing works
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Seuter, S., Neme, A., & Carlberg, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096184 · Cited by 34 · see citing works
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Zheng, H., Zhang, J., Xu, Y., Fine, E. J., Suomivuori, C., Dror, R. O., & Feng, L. (2025) · Nature · doi:10.1038/s41586-025-08667-y · Cited by 33 · see citing works
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Choi, S., Titov, A. A., Sivakumar, R., Li, W., & Morel, L. M. (2016) · Current Rheumatology Reports · doi:10.1007/s11926-016-0615-7 · Cited by 31 · see citing works
Kamm, D. R., Pyles, K. D., Sharpe, M. C., Healy, L. N., Colca, J. R., & McCommis, K. S. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100807 · Cited by 31 · see citing works
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Colca, J. R., McDonald, W. G., & Kletzien, R. F. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12308 · Cited by 31 · see citing works
Self-citationYiew, N. K. H., Vazquez, J. H., Martino, M. R., Kennon‐McGill, S., Price, J. R., Allard, F. D., Yee, E. U., Layman, A. J., James, L. P., McCommis, K. S., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101808 · Cited by 32 · see citing works
Self-citationPower2: The power of yeast genetics applied to the powerhouse of the cell
Rutter, J. P., & Hughes, A. L. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.12.002 · Cited by 29 · see citing works
Rohatgi, N., Aly, H., Marshall, C. A., McDonald, W. G., Kletzien, R. F., Colca, J. R., & McDaniel, M. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062012 · Cited by 29 · see citing works
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Chen, Y., Ma, H., Dasheng, Z., Zhao, G., Wang, L., Fu, X., & Chen, W. (2017) · PPAR Research · doi:10.1155/2017/8360919 · Cited by 29 · see citing works
Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming
Jeong, S. W. (2020) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2020.0115 · Cited by 28 · see citing works
Mitochondrial drug targets in neurodegenerative diseases
Lee, J. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.11.032 · Cited by 26 · see citing works
Hyperglycemia-Induced Endothelial Dysfunction
Gerő, D. (2018) · InTech eBooks · doi:10.5772/intechopen.71433 · Cited by 28 · see citing works
Grattagliano, I., Ciaula, A. D., Baj, J., Molina‐Molina, E., Shanmugam, H., Garruti, G., Wang, D. Q. ‐., & Portincasa, P. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1433-4_12 · Cited by 26 · see citing works
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Colca, J. R., McDonald, W. G., McCommis, K. S., & Finck, B. N. (2017) · Hepatology Communications · doi:10.1002/hep4.1036 · Cited by 23 · see citing works
Self-citationCharacterization of drug-induced human mitochondrial ADP/ATP carrier inhibition
Baron, S. J., King, M. S., Kunji, E. R. S., & Schirris, T. J. J. (2021) · Theranostics · doi:10.7150/thno.54936 · Cited by 24 · see citing works
Identification of protein binding partners of small molecules using label-free methods
Saxena, C. (2016) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2016.1227316 · Cited by 22 · see citing works
Diverse Molecular Targets for Therapeutic Strategies in Alzheimer's Disease
Han, S.-H., & Mook‐Jung, I. (2014) · Journal of Korean Medical Science · doi:10.3346/jkms.2014.29.7.893 · Cited by 22 · see citing works
Li, X., Li, Y., Han, G., Li, X., Ji, Y., Fan, Z., Zhong, Y., Cao, J., Zhao, J., Goscinski, M. A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13210 · Cited by 23 · see citing works
Bardová, K., Funda, J., Pohl, R., Čajka, T., Hensler, M., Kuda, O., Janovská, P., Adamcová, K., Irodenko, I., Lenkova, L., et al. (2020) · Nutrients · doi:10.3390/nu12123737 · Cited by 21 · see citing works
Self-citation
- Authors
- Colca, J. R., McDonald, W. G., Cavey, G. S., Cole, S. L., Holewa, D. D., Brightwell-Conrad, A. S., Wolfe, C. L., Wheeler, J. S., Coulter, K. R., Kilkuskie, P. M., Gracheva, E., Korshunova, Y., Trusgnich, M., Karr, R., Wiley, S. E., Divakaruni, A. S., Murphy, A. N., Vigueira, P. A., Finck, B. N., & Kletzien, R. F.
- Affiliations
- Metabolic Solutions Development Company (United States) (US)
- University of California San Diego (US)
- Washington University in St. Louis (US)
- Corresponding author
- Colca, Jerry R.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-05-15
- Volume
- 8
- Issue
- 5
- Pages
- e61551
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3655167
- OpenAlex
- W2165311378
- Cited by
- 171
- References
- 30
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 9 · 2023: 12 · 2022: 14 · 2021: 12 · 2020: 14 · 2019: 13 · 2018: 15 · 2017: 20 · 2016: 17 · 2015: 8 · 2014: 17 · 2013: 9 · 2012: 1
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Michigan Economic Development Corporation
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA21228, R42AA021228)
- National Institute of Diabetes and Digestive and Kidney Diseases (R41DK084596, DK081298, DK84596, R42DK081298)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- thiazolidinediones, insulin sensitizers, mitochondrial pyruvate carrier, MPC1, MPC2, pyruvate transport, acetyl-CoA biosynthesis, brown adipose tissue, hemolymph glucose, Drosophila melanogaster, drug target identification
- MeSH terms
- Insulin Secretion, Amino Acid Sequence, Animals, Adipose Tissue, Brown, Drosophila melanogaster, Humans, Hypoglycemic Agents, Insulin, Mitochondria, Molecular Sequence Data, Sequence Homology, Amino Acid, Membrane Transport Proteins, Monocarboxylic Acid Transporters, Mitochondrial Membrane Transport Proteins, Thiazolidinediones, Gene Knockdown Techniques, HEK293 Cells
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