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Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy
Open accessAbstract
Mechanisms by which autophagy promotes cell survival or death are unclear. We provide evidence that C(18)-pyridinium ceramide treatment or endogenous C(18)-ceramide generation by ceramide synthase 1 (CerS1) expression mediates autophagic cell death, independent of apoptosis in human cancer cells. C(18)-ceramide-induced lethal autophagy was regulated via microtubule-associated protein 1 light chain 3 β-lipidation, forming LC3B-II, and selective targeting of mitochondria by LC3B-II-containing autophagolysosomes (mitophagy) through direct interaction between ceramide and LC3B-II upon Drp1-dependent mitochondrial fission, leading to inhibition of mitochondrial function and oxygen consumption. Accordingly, expression of mutant LC3B with impaired ceramide binding, as predicted by molecular modeling, prevented CerS1-mediated mitochondrial targeting, recovering oxygen consumption. Moreover, knockdown of CerS1 abrogated sodium selenite-induced mitophagy, and stable LC3B knockdown protected against CerS1- and C(18)-ceramide-dependent mitophagy and blocked tumor suppression in vivo. Thus, these data suggest a new receptor function of ceramide for anchoring LC3B-II autophagolysosomes to mitochondrial membranes, defining a key mechanism for the induction of lethal mitophagy.
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“The localization of CerS1 to the mitochondria and the synthesis of ceramide in the outer mitochondrial membrane recruit the autophagic machinery and induce mitophagy (15) by binding autophagosome-associated LC3.”
From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [15]
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1 retracted
Huang, Q. B., Wu, Y., Tan, H.-L., Ong, C.-N., & Shen, H.-M. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.151 · Cited by 116
RetractedAutophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,615
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Youle, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273
Eaten alive: a history of macroautophagy
Yang, Z., & Klionsky, D. J. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-814 · Cited by 2,155
Rabinowitz, J. D., & White, E. (2010) · Science · doi:10.1126/science.1193497 · Cited by 1,982
Autophagy in mammalian development and differentiation
Mizushima, N., & Levine, B. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-823 · Cited by 1,555
Lindsten, T., Ross, A. J., King, A., Zong, W.-X., Rathmell, J. C., Shiels, H. A., Ulrich, E., Waymire, K. G., Mahar, P., Frauwirth, K., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00136-2 · Cited by 1,489
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., & Tsujimoto, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1192 · Cited by 1,358
Biologically active sphingolipids in cancer pathogenesis and treatment
Öğretmen, B., & Hannun, Y. A. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1411 · Cited by 1,220
Research works printed but not linked: 1
- Shimizu, S. et al. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat. Cell Biol. 6, 1221–1228 (2004). · DOI · Paper page
Cited by
Sorted by citations
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
“Ceramides, positioned at the core of sphingolipid metabolism, play several roles that affect multiple steps of macroautophagy, by inhibition of nutrient transporters,(589) by modulation of BCL2-BECN1 association at the level of AKT signaling,(590) and by regulation of mitophagy.(591) The latter function is regulated b…”
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Mechanism and medical implications of mammalian autophagy
Dikic, I., & Elazar, Z. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0003-4 · Cited by 2,771
Self-consumption: the interplay of autophagy and apoptosis
Mariño, G., Niso-Santano, M., Baehrecke, E. H., & Kroemer, G. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3735 · Cited by 2,172
Sphingolipid metabolism in cancer signalling and therapy
Ogretmen, B. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.96 · Cited by 1,207
Autophagy: Regulator of cell death
Liu, S., Yao, S., Yang, H., Liu, S., & Wang, Y. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06154-8 · Cited by 1,293
Cargo recognition and degradation by selective autophagy
Gatica, D., Lahiri, V., & Klionsky, D. J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0037-z · Cited by 1,067
Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors
Johansen, T., & Lamark, T. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.07.016 · Cited by 736
Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD
Mizumura, K., Cloonan, S. M., Nakahira, K., Bhashyam, A. R., Cervo, M., Kitada, T., Glass, K., Owen, C. A., Mahmood, A., Washko, G. R., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74985 · Cited by 611
“Emerging studies have suggested that mitophagy may be deleterious in a context-specific manner (15).”
BackgroundMitophagy, Mitochondrial Homeostasis, and Cell Fate
Ma, K., Chen, G., Li, W., Kepp, O., Zhu, Y., & Chen, Q. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00467 · Cited by 623
“Thus, LC3– ceramide interactions provoked by ceramide treatment induce mitophagy and can progress to autophagic cell death in human cancer cells (Sentelle et al., 2012).”
BackgroundBasit, F., van Oppen, L. M. P. E., Schöckel, L., Bossenbroek, H. M., Vries, S. E. V. E., Hermeling, J. C., Grefte, S., Kopitz, C., Héroult, M., Willems, P. H. G. M., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.133 · Cited by 574
Emerging views of mitophagy in immunity and autoimmune diseases
Xu, Y., Shen, J., & Ran, Z. (2019) · Autophagy · doi:10.1080/15548627.2019.1603547 · Cited by 533
“Similarly, ceramide (waxy lipid molecules) engages mitophagic machinery through interaction with LC3, leading to inhibition of mitochondrial function and oxygen consumption in tumor cells [67].”
BackgroundSelective autophagy of intracellular organelles: Recent research advances
Li, W., He, P., Huang, Y., Li, Y.-F., Lu, J., Li, M., Kurihara, H., Luo, Z., Meng, T., Onishi, M., et al. (2020) · Theranostics · doi:10.7150/thno.49860 · Cited by 523
“Additionally, ceramide, a bioactive sphingolipid, has been identified as a selective receptor for mitophagy by binding directly to the LC3-II protein [60].”
BackgroundSchulte, M. L., Fu, A., Zhao, P., Li, J., Geng, L., Smith, S. T., Kondo, J., Coffey, R. J., Johnson, M. O., Rathmell, J. C., et al. (2018) · Nature Medicine · doi:10.1038/nm.4464 · Cited by 494
Mitochondrial biogenesis and clearance: a balancing act
Ploumi, C., Daskalaki, I., & Tavernarakis, N. (2016) · FEBS Journal · doi:10.1111/febs.13820 · Cited by 479
Mitophagy in degenerative joint diseases
Sun, K., Jing, X., Guo, J., Yao, X., & Guo, F. (2020) · Autophagy · doi:10.1080/15548627.2020.1822097 · Cited by 471
Mitochondrial autophagy: molecular mechanisms and implications for cardiovascular disease
Li, A., Gao, M. Q., Liu, B., Qin, Y. H., Chen, L., Liu, H., Wu, H., & Gong, G. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04906-6 · Cited by 478
“Drp1 knockdown disrupts ceramide localization in OMM and autophagolysosomes recruitment in tumor cells [78].”
BackgroundMechanisms of Selective Autophagy
Lamark, T., & Johansen, T. (2021) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120219-035530 · Cited by 429
Hamacher‐Brady, A., & Brady, N. R. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2087-8 · Cited by 410
“In addition to protein mitophagy receptors, the lipids ceramide and cardiolipin, when localized to the OMM can directly bind LC3 and engage mitophagy [69, 70].”
BackgroundThe emerging, multifaceted role of mitophagy in cancer and cancer therapeutics
Panigrahi, D. P., Praharaj, P. P., Bhol, C. S., Mahapatra, K. K., Patra, S., Behera, B. P., Mishra, S. R., & Bhutia, S. K. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.07.015 · Cited by 379
Mitophagy: An Emerging Role in Aging and Age-Associated Diseases
Chen, G., Kroemer, G., & Kepp, O. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00200 · Cited by 359
Sphingolipids: regulators of crosstalk between apoptosis and autophagy
Young, M. M., KESTER, M. A., & Wang, H. (2012) · Journal of Lipid Research · doi:10.1194/jlr.r031278 · Cited by 338
The pharmacological regulation of cellular mitophagy
Georgakopoulos, N., Wells, G., & Campanella, M. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2287 · Cited by 330
Caenorhabditis elegans pathways that surveil and defend mitochondria
Liu, Y., Samuel, B. S., Breen, P. C., & Ruvkun, G. (2014) · Nature · doi:10.1038/nature13204 · Cited by 309
Autophagy-dependent cell death—where.; how and why a cell eats itself to death
Bialik, S., Dasari, S. K., & Kimchi, A. (2018) · Journal of Cell Science · doi:10.1242/jcs.215152 · Cited by 295
“In this system, the introduction of a C18 ceramide analog, or overexpression of ceramide synthase 1, led to mitophagy and caspase-independent cell death (Sentelle et al., 2012).”
BackgroundResultInfluentialMitochondrial lipid trafficking
Tatsuta, T., Scharwey, M., & Langer, T. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.07.011 · Cited by 295
Czubowicz, K., Jęśko, H. M., Wencel, P. L., Lukiw, W. J., & Strosznajder, R. P. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1448-3 · Cited by 303
Role and Mechanisms of Mitophagy in Liver Diseases
Ma, X., McKeen, T., Zhang, J., & Ding, W. (2020) · Cells · doi:10.3390/cells9040837 · Cited by 288
“In addition to CL, ceramide, a bioactive sphingolipid, directly binds LC3 to recruit autophagosomes to the mitochondria resulting in cell death, likely due to the induction of lethal mitophagy in cancer cells [63].”
BackgroundMitochondrial degradation: Mitophagy and beyond
Uoselis, L., Nguyen, T. N., & Lazarou, M. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.08.021 · Cited by 270
Mitochondrial quality control in health and in Parkinson’s disease
Eldeeb, M. A., Thomas, R. A., Ragheb, M. A., Fallahi, A., & Fon, E. A. (2022) · Physiological Reviews · doi:10.1152/physrev.00041.2021 · Cited by 281
Mitophagy in Alzheimer’s Disease and Other Age-Related Neurodegenerative Diseases
Cai, Q., & Jeong, Y. Y. (2020) · Cells · doi:10.3390/cells9010150 · Cited by 270
“Additionally, upon Drp1-mediated mitochondrial fission, ceramide was shown to promote autophagic recruitment of mitochondria through direct interaction of ceramide with LC3B-II [71].”
BackgroundMitophagy in Cancer: A Tale of Adaptation
Vara‐Pérez, M., Felipe‐Abrio, B., & Agostinis, P. (2019) · Cells · doi:10.3390/cells8050493 · Cited by 264
“Additionally, ceramides -sphingolipids present in the OMM- can bind LC3B-II to target the mitochondria for degradation upon DRP1-mediated mitochondrial fragmentation [75].”
BackgroundMitophagy and mitochondrial integrity in cardiac ischemia-reperfusion injury
Yang, M., Linn, B. S., Zhang, Y., & Ren, J. T. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.05.007 · Cited by 253
Serine Availability Influences Mitochondrial Dynamics and Function through Lipid Metabolism
Gao, X., Lee, K., Reid, M. A., Sanderson, S. M., Qiu, C., Li, S., Liu, J., & Locasale, J. W. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.017 · Cited by 256
“Cells were divided as previously described (Karbowski et al., 2006) into three categories: “Normal” with >90% of mitochondria forming elongated interconnected networks, “Intermediate” with mixed tubular and short mitochondria, and “Fragmented” with >90% short punctiform mitochondria.”
Regulation of PRKN-independent mitophagy
Terešak, P., Lapão, A., Subic, N., Boya, P., Elazar, Z., & Simonsen, A. (2021) · Autophagy · doi:10.1080/15548627.2021.1888244 · Cited by 256
“In vitro studies using CL-agarose beads showed that DNM1L has a strong binding affinity to CL [135] and cooperate to promote mitochondrial division [140].”
BackgroundInfluentialMitophagy in tumorigenesis and metastasis
Poole, L. P., & Macleod, K. F. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03774-1 · Cited by 257
The Role of Mitophagy in Innate Immunity
Gkikas, I., Palikaras, K., & Tavernarakis, N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01283 · Cited by 248
“To this direction, shortage of mitochondrial population due to induction or persistent mitophagy has also been reported (140, 157, 158).”
BackgroundCeramide is metabolized to acylceramide and stored in lipid droplets
Senkal, C. E., Salama, M. F., Snider, A. J., Allopenna, J. J., Rana, N. A., Koller, A., Hannun, Y. A., & Obeid, L. M. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.02.010 · Cited by 237
“Ceramide, the central molecule in the sphingolipid pathway, regulates various cellular responses such as growth arrest, senescence, apoptosis, and autophagy (Hannun and Obeid, 2008; Mullen et al., 2012; Russo et al., 2012; Sentelle et al., 2012).”
BackgroundSelf-citationMetabolic features of the cell danger response
Naviaux, R. K. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.08.006 · Cited by 243
Law, B. A., Liao, X., Moore, K. S., Southard, A., Roddy, P. L., Ji, R., Szulc, Z. M., Bielawska, A., Schulze, P. C., & Cowart, L. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700300r · Cited by 232
Self-citationNo Parkin Zone: Mitophagy without Parkin
Villa, E., Marchetti, S., & Ricci, J. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.07.004 · Cited by 229
Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases
Chu, C. T. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.07.015 · Cited by 218
A guide to the regulation of selective autophagy receptors
Gubaš, A., & Đikić, I. (2021) · FEBS Journal · doi:10.1111/febs.15824 · Cited by 229
Outstanding Questions in Mitophagy: What We Do and Do Not Know
Montava‐Garriga, L., & Ganley, I. G. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.06.032 · Cited by 218
Dany, M., Gencer, S., Nganga, R., Thomas, R. J., Oleinik, N. V., Baron, K. D., Szulc, Z. M., Ruvolo, P. P., Kornblau, S. M., Andreeff, M., et al. (2016) · Blood · doi:10.1182/blood-2016-04-708750 · Cited by 211
Self-citationGuo, X., Sun, X., Hu, D., Wang, Y.-J., Fujioka, H., Vyas, R., Chakrapani, S., Joshi, A. U., Luo, Y., Mochly-Rosen, D., et al. (2016) · Nature Communications · doi:10.1038/ncomms12646 · Cited by 200
The multifaceted regulation of mitophagy by endogenous metabolites
Zhang, T., Liu, Q., Gao, W., Sehgal, S. A., & Wu, H. (2021) · Autophagy · doi:10.1080/15548627.2021.1975914 · Cited by 209
“The C18-ceramide can localize on mitochondria, where it binds to MAP1LC3 and mediates the phagophore engulfing mitochondria for mitophagy [156,157].”
BackgroundMitochondria as Cellular and Organismal Signaling Hubs
Shen, K., Pender, C. L., Bar‐Ziv, R., Zhang, H., Wickham, K., Willey, E., Durieux, J., Ahmad, Q., & Dillin, A. G. (2022) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120420-015303 · Cited by 214
The role of ceramides in metabolic disorders: when size and localization matters
Turpin-Nolan, S. M., & Brüning, J. C. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0320-5 · Cited by 208
Chen, Y., Chen, H., Wang, K., Zhang, L., Huang, Z., Liu, J., Zhang, Z., Luo, M., Lei, Y., Peng, Y., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.09.022 · Cited by 192
Mitochondrial quality control as a key determinant of cell survival
Sedlackova, L., & Korolchuk, V. I. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.12.012 · Cited by 187
Emerging role of mitophagy in human diseases and physiology
Um, J., & Yun, J. (2017) · BMB Reports · doi:10.5483/bmbrep.2017.50.6.056 · Cited by 185
“apoptosis and senescence, induces mitophagy (76).”
Regulation of Mammalian Mitochondrial Dynamics: Opportunities and Challenges
Yu, R., Lendahl, U., Nistér, M., & Zhao, J. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00374 · Cited by 183
“For instance, ceramide (a bioactive sphingolipid) in the MOM is found to interact with LC3B-II and trigger lethal mitophagy through the selective targeting of LC3B-II-containing autophagosomes to mitochondria (232).”
BackgroundDiverse Functions of Ceramide in Cancer Cell Death and Proliferation
Saddoughi, S. A., & Öğretmen, B. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-394274-6.00002-9 · Cited by 186
Doxorubicin‐induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy
Catanzaro, M. P., Weiner, A., Kaminaris, A., Li, C., Cai, F., Zhao, F., Kobayashi, S., Kobayashi, T., Huang, Y., Sesaki, H., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201802663r · Cited by 181
Shen, Y., Guerra‐Librero, A., Fernández-Gil, B. I., Florido, J., García‐López, S., Martínez-Ruiz, L., Mendivil‐Perez, M., Soto‐Mercado, V., Acuña-Castroviejo, D., Ortega‐Arellano, H. F., et al. (2017) · Journal of Pineal Research · doi:10.1111/jpi.12461 · Cited by 175
Hernández‐Tiedra, S., Fabriàs, G., Dávila, D., Salanueva, Í. J., Casas, J., Montes, L. R., Antón, Z., García-Taboada, E., Salazar‐Roa, M., Lorente, M., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1213927 · Cited by 168
“It is worth noting that ceramides had been previously implicated in autophagy-associated cell death via induction of lethal mitophagy.(44) However, we did not find a significant increase in mitophagy upon treatment with THC (data not shown) indicating that this mechanism is not responsible for the stimulation of autop…”
BackgroundInfluentialCeramide and the mitochondrial respiratory chain
Kogot‐Levin, A., & Saada, A. (2013) · Biochimie · doi:10.1016/j.biochi.2013.07.027 · Cited by 162
Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans
Bergman, B. C., Brozinick, J. T., Strauss, A., Bacon, S., Kerege, A., Bui, H. H., Sanders, P., Siddall, P., Wei, T., Thomas, M. K., et al. (2016) · Diabetologia · doi:10.1007/s00125-015-3850-y · Cited by 148
Selvam, S. P., Palma, R. M. D., Oaks, J. J., Oleinik, N. V., Peterson, Y. K., Stahelin, R. V., Skordalakes, E., Ponnusamy, S., Garrett-Mayer, E. S., Smith, C. D., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aaa4998 · Cited by 155
Self-citationHuang, S., Lü, W., Ge, D., Meng, N., Li, Y., Su, L., Zhang, S., Zhang, Y., Zhao, B., & Miao, J. (2015) · Autophagy · doi:10.1080/15548627.2015.1106663 · Cited by 151
“Furthermore, excessive mitophagy induced by CERS1 is lethal and leads to tumor suppression.(26,47) TGFB2-OT1 downregulation by 3BDO increased MIR3960 levels and reduced those of CERS1, whereas TGFB2-OT1 overexpression downregulated MIR3960 levels and increased the CERS1 protein level (Fig.”
BackgroundThe Role of Mitochondrial Dynamics and Mitophagy in Carcinogenesis, Metastasis and Therapy
Wang, Y., Liu, H., Cao, Y., Zhang, L., Huang, F., & Yi, C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00413 · Cited by 150
Increased de novo ceramide synthesis and accumulation in failing myocardium
Ji, R., Akashi, H., Drosatos, K., Liao, X., Jiang, H., Kennel, P. J., Brunjes, D. L., Castillero, E., Zhang, X., Deng, L. Y., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.96203 · Cited by 154
Lee, J. K., Jin, H. K., Park, M. H., Kim, B.-R., Lee, P. H., Nakauchi, H., Carter, J., He, X., Schuchman, E. H., & Bae, J. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20132451 · Cited by 149
Hou, X., Fiesel, F. C., Truban, D., Castanedes Casey, M., Lin, W.-L., Soto, A. I., Tacik, P., Rousseau, L. G., Diehl, N. N., Heckman, M. G., et al. (2018) · Autophagy · doi:10.1080/15548627.2018.1461294 · Cited by 147
“These include different receptor[46] and lipid-mediated [47,48] pathways that recruit phagophores independent of ubiquitin via direct binding to MAP1LC3A family members.”
BackgroundLong non-coding RNAs involved in autophagy regulation
Yang, L., Wang, H., Shen, Q., Feng, L., & Jin, H. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.464 · Cited by 142
“increased to induce mitophagy (a class of selective autophagy targeting dysfunctional mitochondria) by directly interacting with LC3-II-containing autophagolysosomes upon Drp1dependent mitochondrial fission.(89,91) In summary, ectopic expression of TGFB2-OT1 induced by VEC inflammation triggers activates autophagy via…”
BackgroundPi, H., Xu, S., Zhang, L., Guo, P., Li, Y., Xie, J., Tian, L., He, M., Lu, Y., Li, M., et al. (2013) · Autophagy · doi:10.4161/auto.25665 · Cited by 139
“Mitophagy targets small, round mitochondria for digestion and elimination, whereas mitochondrial elongation can protect the mitochondria from autophagic degradation and can also sustain the ATP levels.(15,16,23) In the present study, we proposed an intriguing mechanism whereby cadmium-induced hepatotoxicity may arise…”
BackgroundInfluentialCeramides in Skin Health and Disease: An Update
Uchida, Y., & Park, K. (2021) · American Journal of Clinical Dermatology · doi:10.1007/s40257-021-00619-2 · Cited by 141
Prieto‐Domínguez, N., Ordóñez, R., Fernández, A., Méndez‐Blanco, C., Baulies, A., García‐Ruiz, C., Fernández-Checa, J. C., Mauriz, J. L., & González‐Gallego, J. (2016) · Journal of Pineal Research · doi:10.1111/jpi.12358 · Cited by 139
A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism
Turner, N. A., Lim, X. Y., Toop, H. D., Osborne, B., Brandon, A. E., Taylor, E. N., Fiveash, C. E., Govindaraju, H., Teo, J. D., McEwen, H. P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05613-7 · Cited by 138
Increased de novo ceramide synthesis and accumulation in failing myocardium
Ji, R., Akashi, H., Drosatos, K., Liao, X., Jiang, H., Kennel, P. J., Brunjes, D. L., Castillero, E., Zhang, X., Deng, L. Y., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.82922 · Cited by 143
Wang, J., Gao, S., Wang, S., Xu, Z., & Wei, L. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s165699 · Cited by 134
“Sentelle et al showed that mitophagy induction promotes tumor cell death via a mechanism involving autophagy.(36) To investigate the specific role of PINK1/ Parkin-mediated mitophagy in ZnO NP-induced toxicity, we transfected cells with GFP-LC3 to locate the autophagosomes and used the red fluorescent PINK1 puncta to…”
The mitochondrial unfolded protein response–synchronizing genomes
Jovaisaite, V., & Auwerx, J. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.12.003 · Cited by 131
Abuhusain, H. J., Matin, A., Qiao, Q., Shen, H. M., Kain, N., Day, B. W., Stringer, B. W., Daniels, B. J., Laaksonen, M. A., Teo, C., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.494740 · Cited by 132
Mitophagy-driven metabolic switch reprograms stem cell fate
Naik, P. P., Birbrair, A., & Bhutia, S. K. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2922-9 · Cited by 134
The enigma of ceramide synthase regulation in mammalian cells
Wegner, M.-S., Schiffmann, S., Parnham, M. J., Geißlinger, G., & Grösch, S. (2016) · Progress in Lipid Research · doi:10.1016/j.plipres.2016.03.006 · Cited by 135
Mitophagy: Link to cancer development and therapy
Kulikov, A. V., Luchkina, E. A., Gogvadze, V. G., & Zhivotovsky, B. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.10.088 · Cited by 132
Wolbachia Modulates Lipid Metabolism in Aedes albopictus Mosquito Cells
Molloy, J., Sommer, U., Viant, M. R., & Sinkins, S. P. (2016) · Applied and Environmental Microbiology · doi:10.1128/aem.00275-16 · Cited by 131
“This hypothesis fits with our current knowledge that activation of autophagy can reduce Wolbachia bacterial density (30) and that accumulated ceramides are able to activate both autophagic and apoptotic pathways by interacting with the mTOR pathway (62, 63) and have been shown to target autophagosomes to mitochondria…”
Ceramide induced mitophagy and tumor suppression
Dany, M., & Öğretmen, B. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.12.039 · Cited by 130
Mitochondrial quality control in intervertebral disc degeneration
Song, Y., Lu, S., Geng, W., Feng, X., Luo, R., Li, G., & Cao, Y. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00650-7 · Cited by 134
Contribution of specific ceramides to obesity-associated metabolic diseases
Hammerschmidt, P., & Brüning, J. C. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04401-3 · Cited by 133
“In the same study, exogenously applied C16:0 ceramides also localized to mitochondria, where they decreased mitochondrial oxygen-consumption rate and induced mitophagy [181].”
Backgroundde la Mata, M., Cotán, D., Oropesa-Ávila, M., Garrido-Maraver, J., Cordero, M. D., Villanueva Paz, M., Delgado Pavón, A., Alcocer-Gómez, E., de Lavera, I., Ybot-González, P., et al. (2015) · Scientific Reports · doi:10.1038/srep10903 · Cited by 126
Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons
Beckmann, N., Sharma, D., Gulbins, E., Becker, K. A., & Edelmann, B. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00331 · Cited by 127
“Some ceramide-interacting proteins are already identified, for instance kinase suppressor of Ras (KSR) (Zhang et al., 1997; Zhou et al., 2002), ceramide-activated protein phosphatase (CAPP) (Dobrowsky et al., 1993; Wolff et al., 1994; Saddoughi et al., 2013), protein kinase C (PKC)-alpha, and -delta (Huwiler et al., 1…”
Gosejacob, D., Jäger, P. S., Dorp, K. V., Frejno, M., Carstensen, A., Köhnke, M., Degen, J., Dörmann, P., & Hoch, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.691212 · Cited by 129
“More directly, mitochondrial C18:0and C16:0-ceramides interact with LC3B to recruit autophagosomes to mitochondria to induce mitophagy (68).”
BackgroundHernandez‐Corbacho, M. J., Salama, M., Canals, D., Senkal, C. E., & Obeid, L. M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.09.019 · Cited by 126
Self-citationDendrogenin A drives LXR to trigger lethal autophagy in cancers
Segala, G., David, M., de Medina, P., Poirot, M. C., Serhan, N., Vergez, F., Mougel, A., Saland, E., Carayon, K., Leignadier, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01948-9 · Cited by 125
Hu, X., Li, Z., Lin, R., Shan, J.-Q., Yu, Q., Wang, R., Liao, L., Yan, W., Zhen, W., Shang, L., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.634690 · Cited by 135
Pienimaeki‐Roemer, A., Kuhlmann, K., Böttcher, A., Konovalova, T., Black, A., Orsó, E., Liebisch, G., Ahrens, M., Eisenacher, M., Meyer, H. E., et al. (2014) · Transfusion · doi:10.1111/trf.12874 · Cited by 128
“2), which incorporates in the outer membrane of mitochondria, forming permeabilizing pores(55) or promoting autophagosome assembly on damaged mitochondrial membrane.(56) Also the mitochondrial lipid marker CL(57) (Fig.”
BackgroundCeramides and mitochondrial fatty acid oxidation in obesity
Fucho, R., Casals, N., Serra, D., & Herrero, L. (2016) · The FASEB Journal · doi:10.1096/fj.201601156r · Cited by 128
Molecular Mechanisms and Regulation of Mammalian Mitophagy
Choubey, V., Zeb, A., & Kaasik, A. (2021) · Cells · doi:10.3390/cells11010038 · Cited by 128
Meyer, N. E., Zielke, S., Michaelis, J. B., Linder, B., Warnsmann, V., Rakel, S., Osiewacz, H. D., Fulda, S., Mittelbronn, M. G. A., Münch, C., et al. (2018) · Autophagy · doi:10.1080/15548627.2018.1476812 · Cited by 123
Molecular Regulation Mechanisms and Interactions Between Reactive Oxygen Species and Mitophagy
Fan, P., Xie, X.-H., Chen, C., Peng, X., Zhang, P., Yang, C. H., & Wang, Y. (2018) · DNA and Cell Biology · doi:10.1089/dna.2018.4348 · Cited by 122
“Ceramide can increase cancer cell death and chemotherapy sensitivity through inducing the formation of lipidated LC3 and then promoting mitophagy in cancer cells (Sentelle et al. , 2012; Dany et al. , 2016).”
Autophagy paradox and ceramide
Jiang, W., & Öğretmen, B. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.09.005 · Cited by 123
Self-citationMitochondrial quality control: Easy come, easy go
Stotland, A. B., & Gottlieb, R. A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.12.041 · Cited by 123
“Sphingolipids are synthesized in the ER but when ceramides are delivered to the OMM, they serve as important binding sites for LC3-II, thereby mediating mitophagy [109].”
BackgroundMitochondria as intracellular signaling platforms in health and disease
Tan, J. X., & Finkel, T. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202002179 · Cited by 123
Advances in determining signaling mechanisms of ceramide and role in disease
Stith, J. L., Velazquez, F. N., & Obeid, L. M. (2019) · Journal of Lipid Research · doi:10.1194/jlr.s092874 · Cited by 116
“tophagosomes to mitochondria to induce lethal mitophagy (19).”
BackgroundMitophagy: A novel perspective for insighting into cancer and cancer treatment
Song, C., Pan, S., Zhang, J., Li, N., & Geng, Q. (2022) · Cell Proliferation · doi:10.1111/cpr.13327 · Cited by 120
“Activation of the ceramide stress pathway can induce mitophagy to promote cell death in HNSCC.(150) In malignant gliomas, ceramide can upregulate BNIP3 expression to induce mitophagy and cause cancer cell death.”
BackgroundLongo, M., Meroni, M., Paolini, E., Macchi, C., & Dongiovanni, P. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154708 · Cited by 114
UPRmt-mediated cytoprotection and organismal aging
Schulz, A. M., & Haynes, C. M. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.03.008 · Cited by 113
“Intriguingly, ceramide is known to accumulate on damaged mitochondria and is also required for early events in mitophagy [99] suggesting a potential role in coordinating both pathways.”
BackgroundLC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs
Iriondo, M. N., Etxaniz, A., Varela, Y. R., Ballesteros, U., Hervás, J. H., Montes, L. R., Goñi, F. M., & Alonso, A. (2022) · Autophagy · doi:10.1080/15548627.2022.2062111 · Cited by 118
“Lipids, such as ceramide [15] or cardiolipin [16], can also serve as damaged mitochondrial signals/receptors.”
Background
Metadata
- Authors
- Sentelle, R. D., Senkal, C. E., Jiang, W., Ponnusamy, S., Gencer, S., Panneer Selvam, S., Ramshesh, V. K., Peterson, Y. K., Lemasters, J. J., Szulc, Z. M., Bielawski, J., & Ogretmen, B.
- Affiliations
- Medical University of South Carolina (US)
- Venue
- Nature Chemical Biology
- Published
- 2012-08-26
- Volume
- 8
- Issue
- 10
- Pages
- 831-838
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3689583
- OpenAlex
- W1981224101
- Cited by
- 539
- References
- 44
- Citations by year
- 2026: 36 · 2025: 44 · 2024: 50 · 2023: 56 · 2022: 35 · 2021: 47 · 2020: 38 · 2019: 37 · 2018: 48 · 2017: 41 · 2016: 32 · 2015: 31 · 2014: 27 · 2013: 15 · 2012: 2
- FWCI
- 17.96
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-11-26)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1c06rr015455-01a1)
- National Institute on Alcohol Abuse and Alcoholism (P50AA011605, 1-P50-AA11605)
- National Cancer Institute (CA088932, R01CA088932, CA097165, P30CA138313)
- National Institute of Diabetes and Digestive and Kidney Diseases (5P30 DK 34987, P30DK034987)
- National Institute of Dental and Craniofacial Research (DE-016572, R01DE016572)
- National Center for Research Resources (C06 RR-015455)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- ceramide, mitophagy, autophagy, LC3B-II, LC3B lipidation, CERS1, autophagic cell death, Drp1, mitochondrial fission, autophagolysosomes, mitochondrial targeting, oxygen consumption, sodium selenite, tumor suppression, cancer cells
- MeSH terms
- Autophagy, Ceramides, Humans, Lipids, Phagosomes, Cell Death, Microscopy, Confocal, Cell Line, Tumor, Mitophagy
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