HEPES Activates a MiT/TFE-dependent Lysosomal-Autophagic Gene Network in Cultured Cells: A Call for Caution
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In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated. Here, we identify HEPES, a chemical buffering agent that is broadly applied in cell culture, as a potent inducer of lysosome biogenesis. Supplementation of HEPES to cell growth media is sufficient to decouple the MiT/TFE family members-TFEB, TFE3 and MITF-from regulatory mechanisms that control their cytosolic retention. Increased MiT/TFE nuclear import in turn drives the expression of a global network of lysosomal-autophagic and innate host-immune response genes, altering lysosomal dynamics, proteolytic capacity, autophagic flux, and inflammatory signaling. In addition, siRNA-mediated MiT/TFE knockdown effectively blunted HEPES-induced lysosome biogenesis and gene expression profiles. Mechanistically, we show that MiT/TFE activation in response to HEPES requires its macropinocytic ingestion and aberrant lysosomal storage/pH, but is independent of MTORC1 signaling. Altogether, our data underscore the cautionary use of chemical buffering agents in cell culture media due to their potentially confounding effects on experimental results.
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HEPES activated lysosomal transcription factors in macrophages, inhibited the prion protein conversion in neural stem cells and affected their viability and differentiation.
“Briefly, HEPES activated lysosomal transcription factors in macrophages (Tol et al., 2018), inhibited the prion protein conversion in neural stem cells and affected their viability and differentiation (Delmouly et al., 2011).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as Tol et al., 2018
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Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · see citing works
Bindea, G., Mlecnik, B., Hackl, H., Charoentong, P., Tosolini, M., Kirilovsky, A., Fridman, W.-H., Pagès, F., Trajanoski, Z., & Galon, J. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp101 · Cited by 6,280 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works
Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue
Duve, C. D., Pressman, B. C., Gianetto, R., Wattiaux, R., & Appelmans, F. (1955) · Biochemical Journal · doi:10.1042/bj0600604 · Cited by 4,176 · see citing works
TFEB Links Autophagy to Lysosomal Biogenesis
Settembre, C., Di Malta, C., Polito, V. A., Arencibia, M. G., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Medina, D., Colella, P., et al. (2011) · Science · doi:10.1126/science.1204592 · Cited by 3,365 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
A Gene Network Regulating Lysosomal Biogenesis and Function
Sardiello, M., Palmieri, M., di Ronza, A., Medina, D. L., Valenza, M., Gennarino, V. A., Di Malta, C., Donaudy, F., Embrione, V., Polishchuk, R. S., et al. (2009) · Science · doi:10.1126/science.1174447 · Cited by 2,543 · see citing works
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464 · see citing works
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076 · see citing works
ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery
Jung, C. H., Jun, C. B., Ro, S.-H., Kim, Y.-M., Otto, N. M., Cao, J., Kundu, M., & Kim, D.-H. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1249 · Cited by 2,025 · see citing works
A lysosome‐to‐nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB
Settembre, C., Zoncu, R., Medina, D. L., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Ferron, M., Karsenty, G., Vellard, M. C., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.32 · Cited by 1,932 · see citing works
Signals from the lysosome: a control centre for cellular clearance and energy metabolism
Settembre, C., Fraldi, A., Medina, D. L., & Ballabio, A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3565 · Cited by 1,689 · see citing works
Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673 · see citing works
Growing roles for the mTOR pathway
Sarbassov, D. D., Ali, S. M., & Sabatini, D. M. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.009 · Cited by 1,556 · see citing works
ULK1·ATG13·FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy
Ganley, I. G., Lam, D., Wang, J., Ding, X., Chen, S., & Jiang, X. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900573200 · Cited by 1,546 · see citing works
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB
Medina, D. L., Paola, S. D., Peluso, I., Armani, A., Stefani, D. D., Venditti, R., Montefusco, S., Rosato, A. S., Prezioso, C., Forrester, A. R., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3114 · Cited by 1,405 · see citing works
GSEA-P : a desktop application for Gene Set Enrichment Analysis
Subramanian, A., Kuehn, H., Gould, J., Tamayo, P., & Mesirov, J. P. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm369 · Cited by 1,380 · see citing works
MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB
Martina, J. A., Chen, Y., Guček, M., & Puertollano, R. (2012) · Autophagy · doi:10.4161/auto.19653 · Cited by 1,360 · see citing works
Roczniak-Ferguson, A., Petit, C. S. V., Froehlich, F., Qian, S., Ky, J., Angarola, B. L., Walther, T. C., & Ferguson, S. M. (2012) · Science Signaling · doi:10.1126/scisignal.2002790 · Cited by 1,358 · see citing works
Sarkar, S., Davies, J. E., Huang, Z., Tunnacliffe, A., & Rubinsztein, D. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609532200 · Cited by 1,142 · see citing works
CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data
Bindea, G., Galon, J., & Mlecnik, B. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt019 · Cited by 1,066 · see citing works
Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways
Palmieri, M., Impey, S., Kang, H., di Ronza, A., Pelz, C., Sardiello, M., & Ballabio, A. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr306 · Cited by 1,022 · see citing works
Araki, N., Johnson, M. T., & Swanson, J. A. (1996) · The Journal of cell biology · doi:10.1083/jcb.135.5.1249 · Cited by 949 · see citing works
Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1
Bar-Peled, L., Schweitzer, L. D., Zoncu, R., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.07.032 · Cited by 918 · cited 1× · see citing works
“Recent advances in this field have uncovered that active RRAG heterodimers target MTORC1 to the lysosomal surface via a mechanism that requires the vacuolar-type H-translocating adenosine triphosphatase (v-ATPase) and Ragulator, a pentameric scaffolding complex that anchors RRAG GTPases to the lysosomal surface [20-22…”
BackgroundTranscriptional control of autophagy-lysosome function drives pancreatic cancer metabolism
Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., et al. (2015) · Nature · doi:10.1038/nature14587 · Cited by 799 · see citing works
Regulation of mTORC1 by amino acids
Bar-Peled, L., & Sabatini, D. M. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.03.003 · Cited by 773 · see citing works
Melanocytes and theMicrophthalmiaTranscription Factor Network
Steingrı́msson, E., Copeland, N. G., & Jenkins, N. A. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.092717 · Cited by 762 · see citing works
Martina, J. A., Diab, H. I., Lishu, L., Jeong-A, L., Patange, S., Raben, N., & Puertollano, R. (2014) · Science Signaling · doi:10.1126/scisignal.2004754 · Cited by 677 · see citing works
Xu, X., Grijalva, A., Skowronski, A., van Eijk, M., Serlie, M. J., & Ferrante, A. W. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.001 · Cited by 523 · see citing works
Plaisier, S. B., Taschereau, R., Wong, J. A., & Graeber, T. G. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq636 · Cited by 468 · see citing works
Hydrogen ion buffers for biological research
Ferguson, W. J., Braunschweiger, K. I., Braunschweiger, W. R., Smith, J. R., McCormick, J. J., Wasmann, C. C., Jarvis, N. P., Bell, D. H., & Good, N. E. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90079-2 · Cited by 467 · see citing works
Lysosomal storage diseases: from pathophysiology to therapy
Parenti, G., Andria, G., & Ballabio, A. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-122313-085916 · Cited by 404 · see citing works
Rag GTPases mediate amino acid–dependent recruitment of TFEB and MITF to lysosomes
Martina, J. A., & Puertollano, R. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201209135 · Cited by 350 · see citing works
Protein kinase C controls lysosome biogenesis independently of mTORC1
Li, Y., Xu, M., Ding, X., Chen, Y., Song, Z., Chen, L., Huang, X., Wang, X., Jian, Y., Tang, G., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3407 · Cited by 348 · see citing works
TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages
Pastore, N., Brady, O. A., Diab, H. I., Martina, J. A., Sun, L., Huynh, T., Lim, J.-A., Zare, H., Raben, N., Ballabio, A., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1179405 · Cited by 331 · see citing works
Innate Host Defense Requires TFEB-Mediated Transcription of Cytoprotective and Antimicrobial Genes
Visvikis, O., Ihuegbu, N., Labed, S. A., Luhachack, L. G., Alves, A.-M. F., Wollenberg, A. C., Stuart, L. M., Stormo, G. D., & Irazoqui, J. E. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.002 · Cited by 330 · see citing works
Sphingolipid lysosomal storage disorders
Platt, F. M. (2014) · Nature · doi:10.1038/nature13476 · Cited by 320 · see citing works
Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans
Folick, A., Oakley, H. D., Yu, Y., Armstrong, E. H., Kumari, M., Sanor, L., Moore, D. D., Ortlund, E. A., Zechner, R., & Wang, M. C. (2015) · Science · doi:10.1126/science.1258857 · Cited by 283 · see citing works
Amyere, M., Payrastre, B., Krause, U., Smissen, P. V. D., Veithen, A., & Courtoy, P. J. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.10.3453 · Cited by 233 · see citing works
Ultrasensitive in situ visualization of active glucocerebrosidase molecules
Witte, M. D., Kallemeijn, W. W., Aten, J., Li, K., Strijland, A., Donker‐Koopman, W. E., van den Nieuwendijk, A. M. C. H., Bleijlevens, B., Kramer, G., Florea, B. I., et al. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.466 · Cited by 231 · see citing works
Self-citationMITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells
Ploper, D., Taelman, V. F., Robert, L., Perez, B. S., Titz, B., Chen, H.-W., Graeber, T. G., von Euw, E., Ribas, A., & De Robertis, E. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424576112 · Cited by 228 · cited 2× · see citing works
“Similarly, by virtue of its ability to induce endo-lysosomal biogenesis, HEPES may pose a confounding factor in cancer stem cell research by potentiating the WNT signaling pathway [18,57].”
BackgroundAutophagy induction by trehalose counter-acts cellular prion-infection
Aguib, Y., Heiseke, A., Gilch, S., Riemer, C., Baier, M., Ertmer, A., & Schätzl, H. M. (2009) · Autophagy · doi:10.4161/auto.5.3.7662 · Cited by 222 · see citing works
Lennon‐Duménil, A., Bakker, A., Maehr, R., Fiebiger, E., Overkleeft, H. S., Rosemblatt, M. S., Ploegh, H. L., & Lagaudrière‐Gesbert, C. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020327 · Cited by 221 · see citing works
Self-citationDiwu, Z. J., Chen, C.-S., Zhang, C., Klaubert, D. H., & Haugland, R. P. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80059-3 · Cited by 212 · see citing works
Aksan, I., & Goding, C. R. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.12.6930 · Cited by 205 · see citing works
Autophagy: Regulation and role in disease
Meijer, A. J., & Codogno, P. (2009) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360903044068 · Cited by 199 · see citing works
THE UPTAKE, STORAGE, AND INTRACELLULAR HYDROLYSIS OF CARBOHYDRATES BY MACROPHAGES
Cohn, Z. A., & Ehrenreich, B. A. (1969) · The Journal of Experimental Medicine · doi:10.1084/jem.129.1.201 · Cited by 192 · see citing works
Canton, J., Schlam, D., Breuer, C., Gütschow, M., Glogauer, M., & Grinstein, S. (2016) · Nature Communications · doi:10.1038/ncomms11284 · Cited by 148 · see citing works
Gekle, M., Drumm, K., Mildenberger, S., Freudinger, R., Gaßner, B., & Silbernagl, S. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.00709.x · Cited by 113 · see citing works
Huan, C., Kelly, M. L., Steele, R., Shapira, I., Gottesman, S. R. S., & Roman, C. A. J. (2006) · Nature Immunology · doi:10.1038/ni1378 · Cited by 92 · see citing works
Trapping of oxidized LDL in lysosomes of K upffer cells is a trigger for hepatic inflammation
Bieghs, V., Walenbergh, S. M. A., Hendrikx, T., van Gorp, P. J., Verheyen, F., Damink, S. W. M. O., Masclee, A., Koek, G. H., Hofker, M. H., Binder, C. J., et al. (2013) · Liver International · doi:10.1111/liv.12170 · Cited by 88 · see citing works
Biochemistry of glycosphingolipid storage disorders: implications for therapeutic intervention.
Aerts, J., Hollak, C., Boot, R., & Groener, A. (2003) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.2003.1273 · Cited by 84 · see citing works
Self-citationLysosomal Biogenesis in Lysosomal Storage Disorders
Karageorgos, L., Isaac, E. L., Brooks, D. A., Ravenscroft, E. M., Davey, R. C. A., Hopwood, J. J., & Meikle, P. J. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3581 · Cited by 82 · see citing works
Dobrowolski, R., Vick, P., Ploper, D., Gumper, I., Snitkin, H., Sabatini, D. D., & Robertis, E. M. D. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.09.026 · Cited by 79 · see citing works
Detection of Protease Activity Using a Fluorescence-Enhancement Globular Substrate
Voss, E. W., Workman, C. J., & Mummert, M. E. (1996) · BioTechniques · doi:10.2144/96202rr06 · Cited by 72 · see citing works
Lysosomal Stress in Obese Adipose Tissue Macrophages Contributes to MITF-Dependent Gpnmb Induction
Gabriel, T. L., Tol, M. J., Ottenhoff, R., van Roomen, C. P. A. A., Aten, J., Claessen, N., Hooibrink, B., de Weijer, B. A., Serlie, M. J. M., Argmann, C., et al. (2014) · Diabetes · doi:10.2337/db13-1720 · Cited by 65 · see citing works
Self-citationHelip‐Wooley, A., & Thoene, J. G. (2003) · Experimental Cell Research · doi:10.1016/j.yexcr.2003.09.003 · Cited by 41 · see citing works
Poole, C., Reilly, H. C., & Flint, M. H. (1982) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02796499 · Cited by 32 · see citing works
Reprogramming of lysosomal gene expression by interleukin-4 and Stat6
Brignull, L. M., Czimmerer, Z., Saidi, H., Dániel, B., Villela, I. V., Bartlett, N. W., Johnston, S. L., Meira, L. B., Nagy, L., & Nohturfft, A. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-853 · Cited by 19 · see citing works
HEPES Inhibits the Conversion of Prion Protein in Cell Culture
Delmouly, K., Belondrade, M., Casanova, D., Milhavet, O., & Lehmann, S. (2011) · Journal of General Virology · doi:10.1099/vir.0.027334-0 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 66 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Zhou, K., Zheng, Z., Li, Y., Han, W., Zhang, J., Mao, Y., Chen, H. A., Zhang, W., Liu, M., Xie, L., et al. (2020) · Theranostics · doi:10.7150/thno.46566 · Cited by 158 · see citing works
Huang, M., Modeste, E. S., Dammer, E. B., Merino, P., Taylor, G., Duong, D. M., Deng, Q., Holler, C. J., Gearing, M., Dickson, D. W., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01037-x · Cited by 100 · see citing works
Van der Lienden, M. J. C., Gaspar, P., Boot, R., Aerts, J. M. F. G., & Van Eijk, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010066 · Cited by 84 · see citing works
Self-citationThe Unique Phenotype of Lipid-Laden Macrophages
van Eijk, M., & Aerts, J. M. F. G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084039 · Cited by 63 · see citing works
Self-citationDeleterious effects of calcium indicators within cells; an inconvenient truth
Bootman, M. D., Allman, S. A., Rietdorf, K., & Bultynck, G. (2018) · Cell Calcium · doi:10.1016/j.ceca.2018.04.005 · Cited by 49 · see citing works
Lysosomal Biogenesis and Implications for Hydroxychloroquine Disposition
Collins, K. P., Witta, S., Coy, J. W., Pang, Y., & Gustafson, D. L. (2020) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.120.000309 · Cited by 25 · see citing works
Toward Best Practices for Controlling Mammalian Cell Culture Environments
Klein, S. G., Steckbauer, A., Alsolami, S. M., Arossa, S., Parry, A. J., Li, M., & Duarte, C. M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.788808 · Cited by 23 · see citing works
Zwitterionic betaines over HEPES as the new generation biocompatible pH buffers for cell culture
Liu, P., Sun, J. Y., Wan, P., Gu, Y., Ji, X., Su, Z. G., Liu, P., & Shen, J. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.12.028 · Cited by 20 · see citing works
Wang, K., Zhou, W., Hu, G., Wang, L., Cai, R., & Tian, T. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04981-8 · Cited by 16 · see citing works
Glycoprotein Non-Metastatic Protein B (GPNMB): The Missing Link Between Lysosomes and Obesity
Bianco, V., & Kratky, D. (2023) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2192-0101 · Cited by 15 · see citing works
Extracellular Acidity Reprograms Macrophage Metabolism and Innate Responsiveness
Jiang, W., Le, J., Wang, P., Cheng, X., Smelkinson, M. G., Dong, W., Yang, C., Chu, Y., Hwang, P. M., Munford, R. S., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100014 · Cited by 12 · see citing works
Huang, P., Liu, Y., Zhao, C., Wang, C., Wang, L., Luo, M., Wang, W., Shan, W., Liu, X., Li, B., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c05640 · Cited by 10 · see citing works
Depping, R., & Seeger, K. (2019) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-018-1518-4 · Cited by 9 · see citing works
Mendola, R. J., Biswas, L., Schindler, K., Walmsley, R. H., Russell, H., Angle, M., & Garrisi, G. J. (2024) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-024-03064-2 · Cited by 8 · see citing works
Glycoprotein non-metastatic melanoma protein B (GPNMB): An attractive target in atherosclerosis
Yu, X., Li, M., Wang, C., & Guan, X. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150386 · Cited by 8 · see citing works
Han, B., Kamogashira, T., Kikuta, S., & Yamasoba, T. (2023) · FEBS Open Bio · doi:10.1002/2211-5463.13714 · Cited by 6 · see citing works
van der Lienden, M. V. D., Aten, J., Boot, R., van Eijk, M., Aerts, J., & Kuo, C.-L. (2022) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30234 · Cited by 5 · see citing works
Self-citationCook, S. R., Badell‐Grau, R. A., Kirkham, E. D., Jones, K. M., Kelly, B. P., Winston, J., Waller‐Evans, H., Allen, N. D., & Lloyd‐Evans, E. (2020) · AMRC Open Research · doi:10.12688/amrcopenres.12903.1 · Cited by 5 · see citing works
Qiu, Y., Zhang, Y., Wu, Z., Huang, J., Chen, B., Xiao, J., & Chen, F. (2025) · The FASEB Journal · doi:10.1096/fj.202402609rr · Cited by 4 · see citing works
Vahlensieck, C., Thiel, C. S., Mosimann, M., Bradley, T., Caldana, F., Polzer, J., Lauber, B. A., & Ullrich, O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021351 · Cited by 4 · see citing works
Lopes, E., Machado-Oliveira, G., Simões, C. G., Ferreira, I. S., Ramos, C., Ramalho, J. S., Soares, M. I. L., Melo, T. M. V. D. P. E., Puertollano, R., Marques, A. R. A., et al. (2023) · Cells · doi:10.3390/cells12242826 · Cited by 2 · see citing works
He, H., Guo, X., Xu, M., Tan, Z., Tan, C., Li, X., Xiang, Z., He, P., Deng, B., Pu, Y., et al. (2026) · Autophagy · doi:10.1080/15548627.2026.2678426 · Cited by 1 · see citing works
Kegel, N. B., Kaufmann, A. M., Matrosovich, M. N., Bauer, S., & Dorna, J. (2024) · Virology · doi:10.1016/j.virol.2024.110314
Huang, M., Modeste, E. S., Dammer, E., Merino, P., Taylor, G., Duong, D. M., Deng, Q., Holler, C. J., Gearing, M., Dickson, D. W., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13064301
Huang, M., Modeste, E. S., Dammer, E., Merino, P., Taylor, G., Duong, D. M., Deng, Q., Holler, C. J., Gearing, M., Dickson, D. W., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13064298
HEPES in Cell Culture Alters the Multi‐Omics Profile Exhibited by Gaucher Disease Fibroblasts
Corazolla, E. M., Schomakers, B. V., Trętowicz, M. M., Hermans, J., van Weeghel, M., Vaz, F. M., Pras‐Raves, M. L., der Vlugt, K. G., Stet, F. S., Goorden, S. M. I., et al. (2026) · Journal of Cellular Biochemistry · doi:10.1002/jcb.70080
Wang, J., 高, 畠., Su, Y., Zhou, B., Zhang, Z., Liu, G., Wang, Q., Shen, S., Fan, S., Ma, J., et al. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.153997
- Authors
- Tol, M. J., van der Lienden, M. J. C., Gabriel, T. L., Hagen, J. J., Scheij, S., Veenendaal, T., Klumperman, J., Donker-Koopman, W. E., Verhoeven, A. J., Overkleeft, H., Aerts, J. M., Argmann, C. A., & van Eijk, M.
- Affiliations
- University of California, Los Angeles (US)
- Leiden Institute of Chemistry, Leiden University, The Netherlands
- Amsterdam UMC Location University of Amsterdam (NL)
- Icahn School of Medicine at Mount Sinai (US)
- University Medical Center Utrecht (NL)
- Department of Medical Biochemistry, University of Amsterdam, Academic Medical Centre, The Netherlands
- Leiden University (NL)
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2018-02-17
- Volume
- 14
- Issue
- 3
- Pages
- 437-449
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC5915011
- OpenAlex
- W2794029136
- Cited by
- 27
- References
- 66
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 6 · 2018: 3
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Autophagy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Figshare (cc-by)
- Funders
- Dutch Diabetes Foundation (2014.00.1758)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- HEPES, TFEB, TFE3, MITF, lysosomal biogenesis, mTORC1, macropinocytosis, lysosomal pH, lysosomal storage, innate immune response, transcriptional regulation
- MeSH terms
- Autophagy, Cell Line, HEPES, Humans, Lysosomes, Signal Transduction, Microphthalmia-Associated Transcription Factor, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Gene Regulatory Networks
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