The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Sensitivity to Lysosome-Dependent Cell Death Is Directly Regulated by Lysosomal Cholesterol Content
Open accessAbstract
Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1) protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2), which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determineD the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Moreover, under physiological conditions, lysosomal membranes can be stabilized by altering lysosomal cholesterol content [788] or by boosting endogenous activity of heat shock protein family A (Hsp70) member 1A (HSPA1A; best known as HSP70) [789, 790].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [788]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lipid rafts as a membrane-organizing principle
Lingwood, D., & Simons, K. (2010) · Science · doi:10.1126/science.1174621 · Cited by 4,417 · cited 1×
“As cholesterol is an important component of all cellular membranes, including specialized lipid raft micro domains [34],”
BackgroundEvidence for the Formation of Symmetric and Asymmetric DLPC-DAPC Lipid Bilayer Domains
Ritter, M., Schmidt, S., Jakab, M., Paulmichl, M., & Henderson, R. M. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350122 · Cited by 3,923
Simons, K., & Ikonen, E. (2000) · Science · doi:10.1126/science.290.5497.1721 · Cited by 1,277 · cited 1×
“Normally, cholesterol is released from endocytosed low density lipoprotein (LDL) particles by the action of lysosomal acid lipase and is then transported, via the lysosomal NPC proteins, to the ER where it serves as a sensor for cellular cholesterol homeostasis and may be esterified [6].”
BackgroundLloyd‐Evans, E., Morgan, A. J., He, X., Smith, D. A., Elliot-Smith, E., Sillence, D. J., Churchill, G. C., Schuchman, E. H., Galione, A., & Platt, F. M. (2008) · Nature Medicine · doi:10.1038/nm.1876 · Cited by 832 · cited 3×
“sphingomyelin, glycosphingolipids and sphingosine [9,22], which have been suggested to influence the stability of lysosomes [26,27].”
BackgroundGuicciardi, M. E., Deussing, J. M., Miyoshi, H., Bronk, S. F., Svingen, P. A., Peters, C., Kaufmann, S. H., & Gores, G. J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9914 · Cited by 710 · cited 1×
“Previous studies have convincingly shown that the presence of lysosomal proteases, cathepsins, in the cytosol mediates apoptosis [2,3,4], implying that the integrity of the lysosomal membrane is of high importance for cell survival.”
BackgroundFoghsgaard, L., Wissing, D., Mauch, D., Lademann, U. A., Bastholm, L., Boes, M. L., Elling, F., Leist, M., & Jäättelä, M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.999 · Cited by 629 · cited 1×
“Previous studies have convincingly shown that the presence of lysosomal proteases, cathepsins, in the cytosol mediates apoptosis [2,3,4], implying that the integrity of the lysosomal membrane is of high importance for cell survival.”
BackgroundRegulation of apoptosis-associated lysosomal membrane permeabilization
Johansson, A., Appelqvist, H., Nilsson, C., Kågedal, K., Roberg, K. B., & Öllinger, K. M. (2010) · APOPTOSIS · doi:10.1007/s10495-009-0452-5 · Cited by 479 · cited 1×
“The mechanism underlying LMP is still incompletely understood; however, a number of factors have been described to affect the stability of the lysosomal membrane, including the level of lysosome-associated membrane proteins (LAMP) and cholesterol [5].”
BackgroundSelf-citationDavidson, C. D., Ali, N. F., Micsenyi, M. C., Stephney, G. W., Renault, S., Dobrenis, K., Ory, D. S., Vanier, M. T., & Walkley, S. U. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006951 · Cited by 449 · cited 1×
“b-Cyclodextrin compounds has been shown to correct cholesterol transport in NPC-defective cells [13] and substantially reduce neurodegeneration and increase lifespan in Npc1 mice [14].”
BackgroundLysosomes and lysosomal cathepsins in cell death
Repnik, U., Stoka, V., Türk, V., & Turk, B. (2011) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2011.08.016 · Cited by 412 · cited 1×
“Lysosomes are acidic organelles involved in several cellular functions, including degradation of macromolecules, repair of the plasma membrane, antigen presentation, recycling of cell surface receptors and apoptosis signaling [1].”
BackgroundSphingosine-induced apoptosis is dependent on lysosomal proteases
Kågedal, K., Ming, Z. H. A. O., Svensson, I., & Brunk, U. T. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590335 · Cited by 379
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Hansson E, Rönnbäck L (1989) Primary cultures of astroglia and neurons from different brain regions. In: Shahar A d, Vernadakis A, Haber B, editors. A dissection and tissue culture manual of nervous system. 1st ed. New York: Liss. pp. 92–104.
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
“siological conditions, lysosomal membranes can be stabilized by altering lysosomal cholesterol content [788] or by boosting endogenous activity of heat shock protein family A (Hsp70) member 1A (HSPA1A; best known as HSP70) [789, 790].”
BackgroundThe role of autophagy in neurodegenerative disease
Nixon, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3232 · Cited by 2,059
The lysosome: from waste bag to potential therapeutic target
Appelqvist, H., Wäster, P., Kågedal, K., & Öllinger, K. (2013) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjt022 · Cited by 772
“Multiple cysteine cathepsins (including cathepsin B, D, H, K, L, and S) activate Bid (Cirman et al., 2004; Heinrich et al., 2004; Caruso et al., 2006; Appelqvist et al., 2012a).”
BackgroundInfluentialLysosomal Biology and Function: Modern View of Cellular Debris Bin
Trivedi, P. C., Bartlett, J. J., & Pulinilkunnil, T. (2020) · Cells · doi:10.3390/cells9051131 · Cited by 309
Gangliosides and Gangliosidoses: Principles of Molecular and Metabolic Pathogenesis
Sandhoff, K., & HARZER, K. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0822-13.2013 · Cited by 283
“Perimeter membranes are protected by a thick glycocalyx enriched in polylactosamine structures, and by a high cholesterol level (Hay, 1989; Appelqvist et al., 2012), the chaperon HSP70 (Kirkegaard et al., 2010), and presumably also by a high lateral pressure attenuating the interaction with GM2AP,…”
Yang, J., Griffin, A. S., Qiang, Z., & Ren, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01243-0 · Cited by 224
“Thus, lysosomal membrane integrity is critical for maintaining cellular homeostasis and regulating cellular physiological functions.(262) Moreover, during apoptosis, lysosomes could interact with mitochondria.”
BackgroundInflammation and Metabolism in Cancer Cell—Mitochondria Key Player
Neagu, M. T., Constantin, C., Popescu, I., Zipeto, D., Tzanakakis, G. N., Nikitovic, D., Fenga, C., Stratakis, C. A., Spandidos, D. A., & Tsatsakis, A. M. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00348 · Cited by 151
Feng, W., Zhou, X., Nie, W., Chen, L., Qiu, K., Zhang, Y., & He, C. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/am508837v · Cited by 140
Lysosomes as Oxidative Targets for Cancer Therapy
Dielschneider, R. F., Henson, E. S., & Gibson, S. B. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/3749157 · Cited by 123
“Various cellular components can protect the lysosome from permeabilization such as cholesterol [28], lysosomal localization of heat shock protein 70 [29], and lipid peroxidation scavengers.”
BackgroundThe Role of Cholesterol in α‐Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease
García‐Sanz, P., Aerts, J. M. F. G., & Moratalla, R. (2020) · Movement Disorders · doi:10.1002/mds.28396 · Cited by 126
Seebacher, N. A., Richardson, D. R., & Jansson, P. J. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.381 · Cited by 111
“We attribute this effect to U18666A stabilizing lysosomal membranes against oxidative stress and also partially inhibiting Pgp activity (Figure 7aiii and aiv), thereby preventing LMP (Figure 8).(14,35) The ability of U18666A to inhibit LMP by Dp44mT or DpC prevents DOX release from lysosomes and avoids nuclear targeti…”
BackgroundResultSphingolipids and lysosomal pathologies
Schulze, H., & Sandhoff, K. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.10.015 · Cited by 114
“The glycocalix is formed by highly N-glycosylated integral membrane proteins [59,60], and stabilized by high cholesterol levels [61,62], and chaperone HSP70 [63].”
BackgroundLysosomal quality control: molecular mechanisms and therapeutic implications
Yang, H., & Tan, J. X. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.01.001 · Cited by 86
Role of autophagy in the pathogenesis of amyotrophic lateral sclerosis
Lee, J. K., Shin, J. H., Lee, J. E., & Choi, E.-J. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.005 · Cited by 91
“The integrity of the lysosomal membrane is compromised under various neuropathologic conditions, suggesting that lysosomal membrane proteins may be potential therapeutic targets [69-71].”
BackgroundKing, M. A., Ganley, I. G., & Flemington, V. (2016) · Oncogene · doi:10.1038/onc.2015.511 · Cited by 80
Ganglioside Metabolism in Health and Disease
Sandhoff, R., Schulze, H., & Sandhoff, K. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.01.002 · Cited by 75
The role of lysosome in cell death regulation
Yu, F., Chen, Z., Wang, B., Zhao, J., Hou, Y., Ma, S., & Liu, X. (2015) · Tumor Biology · doi:10.1007/s13277-015-4516-6 · Cited by 70
“It has been reported that the lysosome stability and the cell death susceptibility could be regulated by cholesterol content in lysosome [3].”
BackgroundMetabolic and cellular bases of sphingolipidoses
Sandhoff, K. (2013) · Biochemical Society Transactions · doi:10.1042/bst20130083 · Cited by 59
Eriksson, I., Nath, S., Bornefall, P., Giraldo, A. M. V., & Öllinger, K. M. (2017) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2017.01.002 · Cited by 57
Self-citationLamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila
Chaudhry, N. Y., Sica, M., Surabhi, S., Hernández, D. S., Mesquita, A., Selimovic, A., Riaz, A., Lescat, L., Bai, H., MacIntosh, G. C., et al. (2022) · Autophagy · doi:10.1080/15548627.2022.2038999 · Cited by 56
“Additionally, degradation of cytoplasmic proteins and organelles via autophagy is critically dependent on lysosomal function, and defective lysosomal proteolysis and autophagosomallysosomal fusion contribute to neurodegenerative diseases including Parkinson, Alzheimer’s and Huntington disease [3,11,12].”
BackgroundRodrigues, D., Viotto, A. C., Checchia, R. G., Gomide, A. B., Severino, D., Itri, R., Baptista, M. S., & Martins, W. K. (2016) · Photochemical & Photobiological Sciences · doi:10.1039/c5pp00409h · Cited by 55
Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation
Wäster, P., Eriksson, I., Vainikka, L. K., Rosdahl, I. K., & Öllinger, K. M. (2016) · Scientific Reports · doi:10.1038/srep27890 · Cited by 56
Self-citationGutierrez, E. M., Seebacher, N. A., Arzuman, L., Kovačević, Ž., Lane, D. J. R., Richardson, V., Merlot, A. M., Lok, H. C., Kalinowski, D. S., Sahni, S., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.04.017 · Cited by 48
Cholesterol Metabolism in Cancer and Cell Death
Chen, F., Lu, Y., Lin, J., Kang, R., & Liu, J. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0340 · Cited by 53
“Lysosomal cholesterol accumulation has been suggested to increase lysosomal membrane stability against oxidative stress-induced apoptosis (Appelqvist et al., 2012).”
Liu, E. A., Schultz, M. L., Mochida, C., Chung, C., Paulson, H. L., & Lieberman, A. P. (2020) · JCI Insight · doi:10.1172/jci.insight.136676 · Cited by 51
“In contrast, studies have also described the importance of lipids in membrane rigidity and lysosomal membrane stability (57-59).”
Lysosomal storage diseases and the heat shock response: convergences and therapeutic opportunities
Ingemann, L., & Kirkegaard, T. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r048090 · Cited by 44
Cholesterol crystals in the pathogenesis of atherosclerosis
Baumer, Y., Irei, J. S., & Boisvert, W. A. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01100-3 · Cited by 45
“Although these results seem promising, excessive cholesterol depletion from lysosomes using methyl-β-cyclodextrin has been shown to induce cell death 185 .”
Lysosomal exocytosis and caspase-8 mediated apoptosis in UVA-irradiated keratinocytes
Appelqvist, H., Wäster, P., Eriksson, I., Rosdahl, I. K., & Öllinger, K. M. (2013) · Journal of Cell Science · doi:10.1242/jcs.130633 · Cited by 38
Self-citationNagakannan, P., Tabeshmehr, P., & Eftekharpour, E. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.04.001 · Cited by 41
Miles, A., Andiappan, M., Upenieks, L., & Orfanidis, C. (2021) · PLoS ONE · doi:10.1371/journal.pone.0245865 · Cited by 48
Kunishige, R., Mizoguchi, M., Tsubouchi, A., Hanaoka, K., Miura, Y., Kurosu, H., Urano, Y., Kuro‐o, M., & Murata, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-77308-3 · Cited by 38
Martins, W. K., Costa, É. T., Cruz, M. C., Stolf, B. S., Miotto, R., Cordeiro, R. M., & Baptista, M. S. (2015) · Scientific Reports · doi:10.1038/srep12425 · Cited by 32
The role of lysosomal ion channels in lysosome dysfunction
Kendall, R. L., & Holian, A. (2021) · Inhalation Toxicology · doi:10.1080/08958378.2021.1876188 · Cited by 38
Gurvich, D. E., Zeballos, S. R., & Demaio, P. H. (2014) · South African Journal of Botany · doi:10.1016/j.sajb.2014.03.018 · Cited by 35
Hu, P., Li, H., Sun, W., Wang, H.-Z., Yu, X.-X., Qing, Y.-J., Wang, Z., Zhu, M.-Y., Xu, J.-Y., Guo, Q.-L., et al. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.02.004 · Cited by 31
“(2): VTumorZ ðShortest diameterÞ(2) ðLongest diameterÞ=2: ð2Þ”
Hydroxypropyl-β-cyclodextrin causes massive damage to the developing auditory and vestibular system
Ding, D., Manohar, S., Jiang, H., & Salvi, R. (2020) · Hearing Research · doi:10.1016/j.heares.2020.108073 · Cited by 33
Valero-Galván, J., González-Fernández, R., Sigala-Hernández, A., Núñez-Gastélum, J. A., Ruíz-May, E., Rodrigo-García, J., Larqué-Saavedra, A., & Martínez–Ruiz, N. D. R. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109909 · Cited by 36
Lysosome quality control in health and neurodegenerative diseases
Ferrari, V., Tedesco, B., Cozzi, M., Chierichetti, M., Casarotto, E., Pramaggiore, P., Cornaggia, L., Mohamed, A. A., Patelli, G., Piccolella, M., et al. (2024) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00633-2 · Cited by 36
Ganglioside Metabolism and Its Inherited Diseases
Breiden, B., & Sandhoff, K. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8552-4_5 · Cited by 33
Wäster, P., Eriksson, I., Vainikka, L. K., & Öllinger, K. M. (2020) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12860 · Cited by 31
“…O R D S extracellular vesicles, keratinocytes, melanocytes, miR21, ultraviolet involved in several central processes in the cell including regulation of cell death, cholesterol homeostasis, and repair of plasma membrane damage (Appelqvist et al., 2012; Settembre, Fraldi, Medina, & Ballabio, 2013).”
BackgroundSelf-citationLysosomal damage due to cholesterol accumulation triggers immunogenic cell death
Alvarez-Valadez, K., Sauvat, A., Diharce, J., Leduc, M., Stoll, G., Guittat, L., Lambertucci, F., Paillet, J., Motiño, O., Ferret, L., et al. (2024) · Autophagy · doi:10.1080/15548627.2024.2440842 · Cited by 32
“Cholesterol plays a critical role in maintaining the integrity of lysosomal membranes in response to certain injuries [43,44].”
Collin, A., Hardonnière, K., Chevanne, M., Vuillemin, J., Podechard, N., Burel, A., Dimanche‐Boitrel, M., Lagadic‐Gossmann, D., & Sergent, O. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.029 · Cited by 28
To give or to take money? The effects of choice on prosocial spending and happiness
Moche, H., & Västfjäll, D. (2021) · The Journal of Positive Psychology · doi:10.1080/17439760.2021.1940248 · Cited by 33
Necroptosis-like Neuronal Cell Death Caused by Cellular Cholesterol Accumulation
Funakoshi, T., Aki, T., Tajiri, M., Unuma, K., & Uemura, K. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.727404 · Cited by 27
“It has also been reported that the accumulation of cholesterol in neuronal cells results in the prevention of lysosomal membrane permeabilization-induced apoptosis (38, 39).”
BackgroundProsocial Behavior and Empathy-Related Responding: Relations to Children’s Well-Being
Spinrad, T. L., & Eisenberg, N. (2017) · Springer eBooks · doi:10.1007/978-3-319-58763-9_18 · Cited by 34
Bilotta, M. T., Abruzzese, M. P., Molfetta, R., Scarno, G., Fionda, C., Zingoni, A., Soriani, A., Garofalo, T., Petrucci, M. T., Ricciardi, M. R., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900319r · Cited by 26
Fogde, D. L., Xavier, C. P. R., Balnytė, K., Holland, L. K. K., Stahl-Meyer, K., Dinant, C., Corcelle–Termeau, E., Pereira‐Wilson, C., Maeda, K., & Jäättelä, M. (2022) · Cells · doi:10.3390/cells11244079 · Cited by 26
Cochlear spiral ganglion neuron degeneration following cyclodextrin-induced hearing loss
Ding, D., Jiang, H., & Salvi, R. (2020) · Hearing Research · doi:10.1016/j.heares.2020.108125 · Cited by 24
Lysosomal Repair in Health and Disease
Xun, J., & Tan, J. X. (2025) · Journal of Cellular Physiology · doi:10.1002/jcp.70044 · Cited by 24
“Cholesterol can increase membrane rigidity and thus provide resistance to lysosomal membrane damage (Radulovic et al. 2022; Appelqvist et al. 2012; Gutierrez et al. 2016).”
Sung, E., Yu, K., Shin, J., Seo, Y., Kim, H., Koog, M. G., Kang, I., Kim, J.-J., Lee, B., Shin, T., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.19976 · Cited by 24
“NPC1-mutated cells displayed high expression levels of lysosomal-associated membrane protein (LAMP), a regulator of lysosomal membrane stability [34].”
BackgroundLipid membranes accelerate amyloid formation in the mouse model of AA amyloidosis
Shariatpanahi, A. V., Hultman, P. A., Öllinger, K. M., Westermark, G. T., & Lundmark, K. (2019) · Amyloid · doi:10.1080/13506129.2019.1576606 · Cited by 21
“Increased intracellular cholesterol levels might impair the function of the lysosomal system and contribute to altered macrophage function [38].”
BackgroundSelf-citationTanaka, Y., Ishitsuka, Y., Yamada, Y., Kondo, Y., Takeo, T., Nakagata, N., Higashi, T., Motoyama, K., Arima, H., Matsuo, M., et al. (2014) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2013.12.003 · Cited by 21
“demonstrated that Npc1 null cells or U18666A-treated cells significantly attenuated cell injury induced by O-methyl-serine dodecylamide hydrochloride, an apoptosis inducer, and hydrogen peroxide, an oxidative stress inducer, and suggested that the Npc1 mutation and inhibition can modulate lysosomal function through an…”
BackgroundKondo, Y., Tokumaru, H., Ishitsuka, Y., Matsumoto, T., Taguchi, M., Motoyama, K., Higashi, T., Arima, H., Matsuo, M., Higaki, K., et al. (2016) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2016.04.014 · Cited by 21
Björklund, M., Aho, T., & Behrmann‐Godel, J. (2015) · Ecology and Evolution · doi:10.1002/ece3.1426 · Cited by 20
Shillington, K. J., Johnson, A. M., Mantler, T., Burke, S. M., & Irwin, J. D. (2021) · Journal of Happiness Studies · doi:10.1007/s10902-021-00379-0 · Cited by 20
Pergande, M. R., Nguyen, T. T. A., Haney, C. A., Davidson, C. D., & Cologna, S. M. (2019) · PROTEOMICS · doi:10.1002/pmic.201800432 · Cited by 18
The Psychological Science of Spending Money
Carter, T. J. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0959-9_10 · Cited by 21
Effects of Titanium Dioxide and Zinc Oxide Nano-materials on Lipid Order in Model Membranes
Sydor, M., Anderson, D. S., Steele, H. B. B., Ross, J. B. A., & Holian, A. (2020) · Biochimica et Biophysica Acta - Biomembranes · doi:10.1016/j.bbamem.2020.183313 · Cited by 16
In vitro cytotoxicity of the ternary PAMAM G3–pyridoxal–biotin bioconjugate
Wołowiec, S., Uram, Ł. S., Szuster, M., Gargasz, K., Wałajtys-Rode, E., & Filipowicz-Rachwał, A. (2013) · International Journal of Nanomedicine · doi:10.2147/ijn.s53254 · Cited by 17
“50 Because increased intra-cellular cholesterol levels and elevated cholesterol synthesis were found in cancer cells, the higher resistance of cancer cells (compared with normal fibroblasts) to the cytotoxic effects of PAMAM and BC-PAMAM observed in current studies could be a result of this…”
Childs, E., Henry, C. M., Canton, J., & Sousa, C. R. E. (2021) · Open Biology · doi:10.1098/rsob.210194 · Cited by 17
“Similarly, endocytic organelle membranes enriched in cholesterol are more resistant to damage [45], while lysosomal membranes, which have low cholesterol content, possess the highest amounts of membrane-stabilizing LAMP and LIMP proteins [46].”
BackgroundBankó, C., Nagy, Z. L., Nagy, M., Szemán-Nagy, G., Rebenku, I., Imre, L., Tiba, A., Hajdú, A., Szöllõsi, J., Kéki, S., et al. (2021) · Cancers · doi:10.3390/cancers13225652 · Cited by 17
NPC1 links cholesterol trafficking to microglial morphology via the gastrosome
Zareba, J., Cattaneo, E. F., Villani, A., Othman, A., Streb, S., & Peri, F. (2024) · Nature Communications · doi:10.1038/s41467-024-52874-6 · Cited by 16
Yasamineh, S., Mehrabani, F. J., Derafsh, E., Cosimi, R. D., Forood, A. M. K., Soltani, S., Hadi, M., & Gholizadeh, O. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03798-7 · Cited by 17
“This data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis [6].”
InfluentialSuzuki, S., Ogawa, M., Miyazaki, M., Ota, K., Kazama, H., Hirota, A., Takano, N., Hiramoto, M., & Miyazawa, K. (2021) · Oncology Reports · doi:10.3892/or.2021.8251 · Cited by 15
“To determine whether lysosomal dysfunction can be directly attributed to non‐canonical death and multiple organelle dysfunctions in PDAC cells, the effects of U18666A, which can reportedly strengthen lysosomal membrane by accumulating cholesterol in the lyso‐ somal membrane (61,62), were analyzed.”
BackgroundGaspar, J., Mathieu, J., & Alvarez, P. J. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-02387-8 · Cited by 17
Approaching a Unified Theory for Particle-Induced Inflammation
Bunderson‐Schelvan, M., Hamilton, R. F., Trout, K. L., Jessop, F., Gulumian, M., & Holian, A. (2015) · Current topics in environmental health and preventive medicine · doi:10.1007/978-4-431-55732-6_3 · Cited by 15
“For example, lysosomal stability is increased by the addition of cholesterol [44–46]; accordingly, reduced lysosomal cholesterol content increases the potential for lysosomal membrane destabilization [47].”
BackgroundCholesterol content regulates silica-induced lysosomal membrane permeability
Sydor, M. J., Kendall, R. L., & Holian, A. (2023) · Frontiers in Toxicology · doi:10.3389/ftox.2023.1112822 · Cited by 16
“Our results with lowered lysosomal cholesterol by DOPGmake sense in the context of previous studies that showed U18666A-induced lysosomal cholesterol accumulation caused a decrease in susceptibility to LMP caused by various agents (Appelqvist et al., 2011; Reiners et al., 2011; Appelqvist et al., 2012).”
BackgroundResultAnimal models for lysosomal storage disorders
Pastores, G. M., Torres, P., & Zeng, B. J. (2013) · Biochemistry (Moscow) · doi:10.1134/s0006297913070043 · Cited by 13
Giraldo, A. M. V., Eriksson, I., Wennmalm, S., Fyrner, T., Ederth, T., & Öllinger, K. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093136 · Cited by 13
“Consequently, fibroblasts from a Niemann Pick’s patient were more resilient to LMP-induced cell death [43], demonstrating that the stabilizing effect of cholesterol can be applied on the lysosomal membrane of living cells.”
BackgroundSelf-citationWellen, B. C. M., Skriner, L. C., Freeman, J. R., Stewart, E., Garcia, A. M., Sapyta, J. J., & Franklin, M. E. (2016) · Child Psychiatry & Human Development · doi:10.1007/s10578-016-0662-3 · Cited by 13
Cheetham‐Wilkinson, I. J., Sivalingam, B., Flitton, C., Flottmann, F., Vehling, L., Drechsler, M., Stojchevska, M., Raimondi, A., Paululat, A., Fröhlich, F., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr7325 · Cited by 13
Patel, A., Bhatt, H., & Patel, B. (2021) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2021.131636 · Cited by 11
Adenosine kinase and ADAL coordinate detoxification of modified adenosines to safeguard metabolism
Ogawa, A., Watanabe, S. P., Ozerova, I., Tsai, A. Y., Kuchitsu, Y., Chong, H. B., Kawakami, T., Fuse, J., Han, W., Kudo, R., et al. (2025) · Cell · doi:10.1016/j.cell.2025.07.041 · Cited by 11
Kemplen, K. R., Sancho, D. D., & Clarke, J. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.03.020 · Cited by 10
Yasser, A. G., Sheldon, F., & Hughes, J. M. (2018) · Ecosphere · doi:10.1002/ecs2.2388 · Cited by 10
Thematic review series: Recent advances in the treatment of lysosomal storage diseases
Shayman, J. A. (2014) · Journal of Lipid Research · doi:10.1194/jlr.e049817 · Cited by 10
Kendall, R. L., & Holian, A. (2023) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2023.151310 · Cited by 9
Carvajal-Oliveros, A., Román-Martínez, C., Reynaud, E., & Martínez‐Martínez, E. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1485414 · Cited by 7
Agonist- and stress-driven compartmentalized phosphoinositide signaling in cells
Chen, M., Tan, J. X., Sun, Y., Thapa, N., Cryns, V. L., & Anderson, R. A. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2025.159662 · Cited by 8
Different types of cell death in vascular diseases
Saberianpour, S., Karimi, A., Modaghegh, M.-H. S., & Ahmadi, M. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06402-0 · Cited by 9
Chen, P., Cao, X., Dong, J., Zhao, J., & Wang, F. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c00140 · Cited by 6
Gutay‐Tóth, Z., Gellén, G., Doan, M., Eliason, J. F., Vincze, J., Szente, L., Fenyvesi, F., Goda, K., Vecsernyés, M., Szabó, G., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512335 · Cited by 6
“We recognized that the stability of lysosomes is influenced by acute modulations of PM cholesterol in minutes (Figure 6) and not only on the longer time scale of hours or days, as described in [93].”
BackgroundMethodInfluentialCell Death: a Molecular Perspective
Zia, Q., Azhar, A., Hassan, N., Jain, P., Singh, M., Mirza, M. A., Ali, A., Parveen, S., Hasan, S., Alothaim, A. S., et al. (2021) · Current Molecular Biology Reports · doi:10.1007/s40610-021-00146-3 · Cited by 6
Brain cholesterol homeostasis in Wilson disease
Cacciatore, S., & Tenori, L. (2013) · Medical Hypotheses · doi:10.1016/j.mehy.2013.10.018 · Cited by 6
“Moreover, neurons with lysosomal cholesterol accumulation are protected from oxidative stress-induced apoptosis [19].”
BackgroundTargeting Lysosomes: A Strategy Against Chemoresistance in Cancer
Shirbhate, E., Singh, V. P., Mishra, A., Jahoriya, V., Veerasamy, R., Tiwari, A. K., & Rajak, H. (2024) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/0113895575287242240129120002 · Cited by 5
Zhang, J., Liu, S., Li, L., Wang, G., Liu, F., Zhao, Y., Jing, Y., & Li, Z. (2020) · Journal of Food Biochemistry · doi:10.1111/jfbc.13168 · Cited by 4
Ogundele, O. M., Balogun, W. G., Cobham, A. E., Olakunle, I. A., & Abdulbasit, A. (2016) · Drug and Chemical Toxicology · doi:10.1080/01480545.2016.1188300 · Cited by 3
“Subsequently, the cytoplasmic ROS induce damage to nuclear and lysosomal membranes thereby exposing the nucleus to NO and lysosomal (hydrolytic) enzymes (Appelqvist et al., 2012; Hwang et al., 2010; Violetta et al., 2009).”
BackgroundDealing with damaged lysosomes : Impact of lysosomal membrane stability in health and disease
Eriksson, I. (2022) · Linköping University medical dissertations · doi:10.3384/9789179291792 · Cited by 3
Koshman, V. E., Dmitriev, A. A., Timoshnikov, V. A., Arkhipova, A. S., Selyutina, O. Y., & Polyakov, N. E. (2025) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2025.110390 · Cited by 4
Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets
Luo, T., Wang, C., Zhou, N., ZHANG, Y., & Mou, X. (2026) · Molecules · doi:10.3390/molecules31132373 · Cited by 2
“Its membrane is enriched in cholesterol, a feature that enhances membrane stability and protects against oxidative damage [30].”
Impairment of lipid homoeostasis causes accumulation of protein aggregates in the lysosomePreprint
Yong, J., Villalta, J. E., Vu, N., Kukurugya, M. A., Bennett, B. D., López, M. P., Lazzari-Dean, J. R., Hake, K., & Jan, C. H. (2023) · eLife · doi:10.7554/elife.86194.1 · Cited by 2
Cholesterol-Based Lipid Nanoparticles as an Intracellular Drug Reservoir for Enhanced Tumor Therapy
Jiang, Q., Qiu, Y., Li, P., Yu, C., Meng, T., HU, F., Wang, C., & Yuan, H. (2026) · Pharmaceutical Research · doi:10.1007/s11095-026-04035-1 · Cited by 1
Surviving Stress with the Tumour Microenvironment: Understanding Complex Cell - Cell Interactions
Dawson, R. (2021) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.15102033 · Cited by 2
Surviving Stress with the Tumour Microenvironment: Understanding Complex Cell - Cell Interactions
Dawson, R. (2021) · doi:10.26686/wgtn.15102033.v1 · Cited by 1
Role of lysosome-associated membrane protein, Lamp1, in Drosophila melanogaster
Chaudhry, N. Y. (2023) · doi:10.31274/td-20240617-261 · Cited by 1
The Lysosome -A Central Hub for Cellular Function and Dysfunction
Öllinger, K. M., & Appelqvist, H. (2017) · Journal of Cell Signaling · doi:10.4172/2576-1471.1000143
“Thus, lysosomal cholesterol content is able to influence both sensitivity to LMP and lysosomal exocytosis [20,31].”
BackgroundSelf-citationTargeting Susceptible Signaling Pathways in Chronic Lymphocytic Leukemia
Dielschneider, R. F. (2014) · Mspace (University of Manitoba)
Role of lysosomes in oxidative stress induced regulated cell death
Nagakannan, P. (2020) · Mspace (University of Manitoba)
Targeting epigenetic modifiers in breast cancer
Casciello, F. (2020) · Queensland University of Technology · doi:10.5204/thesis.eprints.200821
Wicks, I. P., Kim, M. L., Souza, D. P. D., Narayana, V. K., Nguyen, N. C., & Sleebs, B. E. (2022) · Research Square · doi:10.21203/rs.3.rs-2299218/v1
Metadata
- Authors
- Appelqvist, H., Sandin, L., Björnström, K., Saftig, P., Garner, B., Öllinger, K., & Kågedal, K.
- Affiliations
- Linköping University (SE)
- University of Wollongong (AU)
- Corresponding author
- Appelqvist, Hanna
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-11-16
- Volume
- 7
- Issue
- 11
- Pages
- e50262
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3500374
- OpenAlex
- W2033615443
- Cited by
- 108
- References
- 46
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 13 · 2022: 5 · 2021: 13 · 2020: 14 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 7 · 2013: 9
- FWCI
- 4.93
- 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)
- Research Online (University of Wollongong) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Figshare (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Vetenskapsrådet (2010-03463)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- lysosomal cholesterol, lysosome-dependent cell death, apoptosis, lysosomal membrane stability, lysosomal membrane permeabilization, Niemann-Pick disease type C1, NPC1 protein, cholesterol accumulation, lipid homeostasis, neurodegenerative diseases, oxidative stress, myriocin, methyl-β-cyclodextrin, 25-hydroxycholesterol, LAMP2, neurons, fibroblasts
- MeSH terms
- Niemann-Pick C1 Protein, Androstenes, Carrier Proteins, Cholesterol, Fibroblasts, Flow Cytometry, Humans, Hydroxycholesterols, Immunohistochemistry, Lysosomes, Membrane Glycoproteins, Microscopy, Phase-Contrast, Mutation, Neurons, Quinacrine, Blotting, Western, Cell Death, Statistics, Nonparametric, beta-Cyclodextrins, Intracellular Signaling Peptides and Proteins, Lysosomal Membrane Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
