Selected publications
2024
Segura-Roman, A., Citron, Y.R., Shin, M., Sindoni, N., Maya-Romero, A., Rapp, S., Goul, C., Mancias, J.D., Zoncu, R., 2024. Autophagosomes coordinate an AKAP11-dependent regulatory checkpoint that shapes neuronal PKA signaling. BioRXiv https://doi.org/10.1101/2024.08.06.606738
Lehmer, M., Zoncu, R., 2024. mTORC1 Signaling Inhibition Modulates Mitochondrial Function in Frataxin Deficiency. BioRXiv. https://doi.org/10.1101/2024.08.06.606942
2023
Goul, C., Peruzzo, R. & Zoncu, R. The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease. Nat Rev Mol Cell Biol (2023) doi:10.1038/s41580-023-00641-8.
Zoncu, R. & Perera, R. M. Emerging roles of the MiT/TFE factors in cancer. Trends Cancer S2405-8033(23)00106–1 (2023) doi:10.1016/j.trecan.2023.06.005.
2022
Shin, H.R., Citron, Y.R., Wang, L., Tribouillard, L., Goul, C.S., Stipp, R., Sugasawa, Y., Jain, A., Samson, N., Lim, C.-Y., Davis, O.B., Castaneda-Carpio, D., Qian, M., Nomura, D.K., Perera, R.M., Park, E., Covey, D.F., Laplante, M., Evers, A.S., Zoncu, R., 2022. Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1. Science 377, 1290–1298.
Jansen, R.M., Peruzzo, R., Fromm, S.A., Yokom, A.L., Zoncu, R., Hurley, J.H., 2022. Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation. Sci Adv 8, eadd2926. https://doi.org/10.1126/sciadv.add2926
Jain A, Zoncu R. Organelle transporters and inter-organelle communication as drivers of metabolic regulation and cellular homeostasis. Mol Metab. 2022 Jun;60:101481.
Zoncu R, Perera RM. Built to last: lysosome remodeling and repair in health and disease. Trends Cell Biol. 2022 Jul;32(7):597–610.
2021
Gupta, S., Yano, J., Mercier, V., Htwe, H.H., Shin, H.R., Rademaker, G., Cakir, Z., Ituarte, T., Wen, K.W., Kim, G.E., Zoncu, R., Roux, A., Dawson, D.W., Perera, R.M., 2021. Lysosomal retargeting of Myoferlin mitigates membrane stress to enable pancreatic cancer growth. Nat Cell Biol 23, 232–242. https://doi.org/10.1038/s41556-021-00644-7
Moldavski, O., Zushin, P.-J.H., Berdan, C.A., Van Eijkeren, R.J., Jiang, X., Qian, M., Ory, D.S., Covey, D.F., Nomura, D.K., Stahl, A., Weiss, E.J., Zoncu, R.¶, 2021. 4β-hydroxycholesterol is a pro-lipogenic factor that promotes SREBP1c expression and activity through Liver X-receptor. J Lipid Res 100051. https://doi.org/10.1016/j.jlr.2021.100051
Davis, O.B., Shin, H.R., Lim, C.-Y., Wu, E.Y., Kukurugya, M., Maher, C.F., Perera, R.M., Ordonez, M.P., Zoncu, R.¶, 2021. NPC1-mTORC1 Signaling Couples Cholesterol Sensing to Organelle Homeostasis and Is a Targetable Pathway in Niemann-Pick Type C. Dev Cell 56, 260-276.e7. https://doi.org/10.1016/j.devcel.2020.11.016
2020
Su, M.-Y., Fromm, S.A., Zoncu, R., Hurley, J.H., 2020. Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD. Nature 585, 251–255. https://doi.org/10.1038/s41586-020-2633-x
Higuchi-Sanabria, R., Shen, K., Kelet, N., Frankino, P.A., Durieux, J., Bar-Ziv, R., Sing, C.N., Garcia, E.J., Homentcovschi, S., Sanchez, M., Wu, R., Tronnes, S.U., Joe, L., Webster, B., Ahilon-Jeronimo, A., Monshietehadi, S., Dallarda, S., Pender, C., Pon, L.A., Zoncu, R., Dillin, A., 2020. Lysosomal recycling of amino acids affects ER quality control. Sci Adv 6, eaaz9805. https://doi.org/10.1126/sciadv.aaz9805.
Shin HR, Zoncu R¶. The Lysosome at the Intersection of Cellular Growth and Destruction. Dev Cell. 2020 Jun 30;
Citron YR, Zoncu R¶. A zinc-sensing protein gives flies a gut feeling for growth. Nature. 2020;580(7802):187–8.
Bindesbøll, C., Aas, A., Ogmundsdottir, M.H., Pankiv, S., Reine, T., Zoncu, R., Simonsen, A., 2020. NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease. Sci Rep 10, 4528. https://doi.org/10.1038/s41598-020-61352-0
2019
Lawrence, R.E*., Fromm, S.A*., Fu, Y., Yokom, A.L., Kim, D.J., Thelen, A.M., Young, L.N., Lim, C.-Y., Samelson, A.J., Hurley, J.H¶, Zoncu, R¶., 2019. Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex. Science. https://doi.org/10.1126/science.aax0364
Lim, C.-Y., Davis, O.B., Shin, H.R., Zhang, J., Berdan, C.A., Jiang, X., Counihan, J.L., Ory, D.S., Nomura, D.K., Zoncu, R¶., 2019. ER-lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann-Pick type C. Nat. Cell Biol. 21, 1206–1218. https://doi.org/10.1038/s41556-019-0391-5 . (read here: https://rdcu.be/bRIg1).
Chung CY, Shin HR, Berdan CA, Ford B, Ward CC, Olzmann JA, Zoncu R¶, Nomura DK¶. Covalent targeting of the vacuolar H+-ATPase activates autophagy via mTORC1 inhibition. Nat Chem Biol. 2019 Aug;15(8):776-785.
Citron YR, Zoncu R¶. Rhomboids Distort Time and Space: Accelerated Proteolysis through Membrane Disruption. Biochemistry. 2019 Apr 23;58(16):2093-2094.
Lawrence, R.E, Zoncu, R¶. The lysosome as a cellular center for signaling, metabolism and quality control. Nat Cell Biol. 2019 Feb;21(2):133-142.
2018
Lawrence RE, Cho KF, Rappold R, Thrun A, Tofaute M, Kim DJ, Moldavski O, Hurley JH, Zoncu R¶. A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold. Nature Cell Biology. 2018;20(9):1052-63.
Shin HR, Zoncu R¶. Finding Sugar in the Pantry: How Galectins Detect and Signal Lysosomal Damage. Mol Cell 2018 Apr 5;70(1):5-7
2017
Su MY, Morris KL, Kim DJ, Fu Y, Lawrence R, Stjepanovic G, Zoncu R¶, Hurley JH¶. Hybrid Structure of the RagA/C-Ragulator mTORC1 Activation Complex. Mol Cell. 2017;68(5):835-46 e3. PMCID: PMC5722659.
Thelen AM, Zoncu R¶. Emerging Roles for the Lysosome in Lipid Metabolism. Trends Cell Biol. 2017
Nguyen TB, Louie SM, Daniele JR, Tran Q, Dillin A, Zoncu R, Nomura DK, Olzmann JA. DGAT1-Dependent Lipid Droplet Biogenesis Protects Mitochondrial Function during Starvation-Induced Autophagy. Developmental Cell. 2017;42(1):9-21 e5.
Di Malta C, Siciliano D, Calcagni A, Monfregola J, Punzi S, Pastore N, Eastes AN, Davis O, De Cegli R, Zampelli A, Di Giovannantonio LG, Nusco E, Platt N, Guida A, Ogmundsdottir MH, Lanfrancone L, Perera RM, Zoncu R, Pelicci PG, Settembre C, Ballabio A. Transcriptional activation of RagD GTPase controls mTORC1 and promotes cancer growth. Science. 2017;356(6343):1188-92.
Castellano BM*, Thelen AM*, Moldavski O, Feltes M, van der Welle RE, Mydock-McGrane L, Jiang X, van Eijkeren RJ, Davis OB, Louie SM, Perera RM, Covey DF, Nomura DK, Ory DS, Zoncu R¶ Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex. Science. 2017;355(6331):1306-11. (pubmed) (PDF)
Belyy, V., Shih, S.M., Bandaria, J., Huang, Y., Lawrence, R.E., Zoncu, R., and Yildiz, A. (2017). PhotoGate microscopy to track single molecules in crowded environments. Nat Commun 8, 13978.
2016
Manifava M., Smith M, Rotondo S, Walker S, Niewczas I, Zoncu R, Clark J, and Ktistakis NT. (2016). Dynamics of mTORC1 activation in response to amino acids. Elife 5.
Lim, C. Y. and Zoncu, R¶ (2016). The lysosome as a command-and-control center for cellular metabolism. J Cell Biol 214(6): 653-664.
Perera RM¶, and Zoncu R¶. (2016). The Lysosome as a Regulatory Hub. Annu Rev Cell Dev Biol.
Young, L.N., Cho, K., Lawrence, R., Zoncu, R., and Hurley, J.H. (2016). Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy. Proceedings of the National Academy of Sciences of the United States of America 113, 8224-8229.
Okosun J, Wolfson RL, Wang J, Araf S, Wilkins L, Castellano BM, Escudero-Ibarz L, Al Seraihi AF, Richter J, Bernhart SH, Efeyan A, Iqbal S, Matthews J, Clear A, Guerra-Assuncao JA, Bodor C, Quentmeier H, Mansbridge C, Johnson P, Davies A, Strefford JC, Packham G, Barrans S, Jack A, Du MQ, Calaminici M, Lister TA, Auer R, Montoto S, Gribben JG, Siebert R, Chelala C, Zoncu R, Sabatini DM, Fitzgibbon J. Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma. Nature genetics. 2016;48(2):183-8. PMCID: 4731318.
2015
Wheeler DB, Zoncu R, Root DE, Sabatini DM, Sawyers CL. Identification of an oncogenic RAB protein. Science. 2015;350(6257):211-7. PMCID: 4600465.
Perera, R.M., Stoykova, S., Nicolay, B.N., Ross, K., Fitamant, J., Buokhali, M., Lengrand, J. Deshpande, V., Selig, M., Ferrone, C.R., Settleman, J., Stephanopoulos, G., Dyson, N.J., Zoncu, R., Ramaswamy, S., Haas, W., Bardeesy, N. (2015) Transcriptional control of the autophagy-lysosomal system drives amino acid metabolism in pancreatic cancer. Nature, doi:10.1038/nature14587.
Katajisto P, Dohla J, Chaffer CL, Pentinmikko N, Marjanovic N, Iqbal S, Zoncu R, Chen W, Weinberg RA, Sabatini DM. Stem cells. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science. 2015;348(6232):340-3. PMCID: 4405120.
Tooze S, Zoncu R¶. Control of cellular homeostasis: organelles take the pilot's seat. Molecular biology of the cell. 2015;26(6):1009-10. PMCID: 4357499.
Wang S, Tsun ZY, Wolfson RL, Shen K, Wyant GA, Plovanich ME, Yuan ED, Jones TD, Chantranupong L, Comb W, Wang T, Bar-Peled L, Zoncu R, Straub C, Kim C, Park J, Sabatini BL, Sabatini DM. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science. 2015;347(6218):188-94. PMCID: 4295826.
Pre-Berkeley
2013
Tsun ZY, Bar-Peled L, Chantranupong L, Zoncu R, Wang T, Kim C, Spooner E, Sabatini DM. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Molecular cell. 2013;52(4):495-505. PMCID: 3867817.
Sahay G, Querbes W, Alabi C, Eltoukhy A, Sarkar S, Zurenko C, Karagiannis E, Love K, Chen D, Zoncu R, Buganim Y, Schroeder A, Langer R, Anderson DG. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nature biotechnology. 2013;31(7):653-8. PMCID: 3814166.
Efeyan A, Zoncu R, Chang S, Gumper I, Snitkin H, Wolfson RL, Kirak O, Sabatini DD, Sabatini DM. Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature. 2013;493(7434):679-83. PMCID: 4000705.
2012
Bar-Peled L, Schweitzer LD, Zoncu R, Sabatini DM. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell. 2012;150(6):1196-208. PMCID: 3517996.
Efeyan A, Zoncu R¶, Sabatini DM¶. Amino acids and mTORC1: from lysosomes to disease. Trends in molecular medicine. 2012;18(9):524-33. PMCID: 3432651.
Settembre C*, Zoncu R*, Medina DL, Vetrini F, Erdin S, Erdin S, Huynh T, Ferron M, Karsenty G, Vellard MC, Facchinetti V, Sabatini DM, Ballabio A. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. The EMBO journal. 2012;31(5):1095-108. PMCID: 3298007.
2011
Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science. 2011;334(6056):678-83. PMCID: 3211112.
Zoncu R, Sabatini DM. Cell biology. The TASCC of secretion. Science. 2011;332(6032):923-5. PMCID: 3390253.
Sheen JH, Zoncu R, Kim D, Sabatini DM. Defective regulation of autophagy upon leucine deprivation reveals a targetable liability of human melanoma cells in vitro and in vivo. Cancer cell. 2011;19(5):613-28. PMCID: 3115736.
Zoncu R*, Efeyan A*, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nature reviews Molecular cell biology. 2011;12(1):21-35. PMCID: 3390257.
2010
Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell. 2010;141(2):290-303. PMCID: 3024592.
Nakatsu F, Perera RM, Lucast L, Zoncu R, Domin J, Gertler FB, Toomre D, De Camilli P. The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics. The Journal of cell biology. 2010;190(3):307-15. PMCID: 2922640.
2009
Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P. A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. The EMBO journal. 2009;28(13):1831-42. PMCID: 2711190.
Zoncu R*, Perera RM*, Balkin DM, Pirruccello M, Toomre D, De Camilli P. A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Cell. 2009;136(6):1110-21. PMCID: 2705806.
2008
Diaz ME, Ayala G, Leon T, Zoncu R, Toomre D. Analyzing protein-protein spatial-temporal dependencies from image sequences using fuzzy temporal random sets. Journal of computational biology : a journal of computational molecular cell biology. 2008;15(9):1221-36.
Diaz E, Sebastian R, Ayala G, Diaz ME, Zoncu R, Toomre D, Gasman S. Measuring spatiotemporal dependencies in bivariate temporal random sets with applications to cell biology. IEEE transactions on pattern analysis and machine intelligence. 2008;30(9):1659-71.
2007
Perera RM, Zoncu R, Johns TG, Pypaert M, Lee FT, Mellman I, Old LJ, Toomre DK, Scott AM. Internalization, intracellular trafficking, and biodistribution of monoclonal antibody 806: a novel anti-epidermal growth factor receptor antibody. Neoplasia. 2007;9(12):1099-110. PMCID: 2134906.
Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D, De Camilli P. A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway. Developmental cell. 2007;13(3):377-90. PMCID: 2025683.
Zoncu R, Perera RM, Sebastian R, Nakatsu F, Chen H, Balla T, Ayala G, Toomre D, De Camilli PV. Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(10):3793-8. PMCID: 1805489.
2006
Sebastian R, Diaz ME, Ayala G, Zoncu R, Toomre D. Analysis of spatial dependencies of endocytic proteins based on temporal random sets. Conference proceedings : Annual International Conference of the IEEE Engineering in Medicine and Biology Society. 2006;1:4175-8.
Perera RM, Zoncu R, Lucast L, De Camilli P, Toomre D. Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(51):19332-7. PMCID: 1693868.
Ayala G, Sebastian R, Diaz ME, Diaz E, Zoncu R, Toomre D. Overlapping events with application to image sequences. IEEE transactions on pattern analysis and machine intelligence. 2006;28(10):1707-12.
2002
Di Paolo G, Pellegrini L, Letinic K, Cestra G, Zoncu R, Voronov S, Chang S, Guo J, Wenk MR, De Camilli P. Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin. Nature. 2002;420(6911):85-9.
Letinic K, Zoncu R, Rakic P. Origin of GABAergic neurons in the human neocortex. Nature. 2002;417(6889):645-9.
* equal contributors ¶ corresponding author