{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:51:22Z","timestamp":1790358682578,"version":"4.1.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K23799"],"award-info":[{"award-number":["JP19K23799"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Foundation for Pharmaceutical Sciences","award":["Grant"],"award-info":[{"award-number":["Grant"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["PRIME"],"award-info":[{"award-number":["PRIME"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human hepatoblastoma cell line, HepG2, has been used for investigating a wide variety of physiological and pathophysiological processes. However, less information is available about the phospholipid metabolism in HepG2 cells. In the present report, to clarify the relationship between cell growth and phospholipid metabolism in HepG2 cells, we examined the phospholipid class compositions of the cells and their intracellular organelles by using enzymatic fluorometric methods. In HepG2 cells, the ratios of all phospholipid classes, but not the ratio of cholesterol, markedly changed with cell growth. Of note, depending on cell growth, the phosphatidic acid (PA) ratio increased and phosphatidylcholine (PC) ratio decreased in the nuclear membranes, the sphingomyelin (SM) ratio increased in the microsomal membranes, and the phosphatidylethanolamine (PE) ratio increased and the phosphatidylserine (PS) ratio decreased in the mitochondrial membranes. Moreover, the mRNA expression levels of enzymes related to PC, PE, PS, PA, SM and cardiolipin syntheses changed during cell growth. We suggest that the phospholipid class compositions of organellar membranes are tightly regulated by cell growth. These findings provide a basis for future investigations of cancer cell growth and lipid metabolism.<\/jats:p>","DOI":"10.1038\/s41598-021-81733-3","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T11:06:44Z","timestamp":1612177604000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Alterations in cellular and organellar phospholipid compositions of HepG2 cells during cell growth"],"prefix":"10.1038","volume":"11","author":[{"given":"Tokuji","family":"Tsuji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ya","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiho","family":"Kambe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Terada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"81733_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394\u2013424 (2018).","journal-title":"CA Cancer J. Clin."},{"key":"81733_CR2","doi-asserted-by":"publisher","first-page":"E926","DOI":"10.3390\/cancers11070926","volume":"11","author":"W Wang","year":"2019","unstructured":"Wang, W., Smits, R., Hao, H. & He, C. Wnt\/beta-catenin signaling in liver cancers. Cancers (Basel) 11, E926 (2019).","journal-title":"Cancers (Basel)"},{"key":"81733_CR3","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.3390\/cancers11101406","volume":"11","author":"N Mavila","year":"2019","unstructured":"Mavila, N. & Thundimadathil, J. The emerging roles of cancer stem cells and Wnt\/Beta-Catenin signaling in hepatoblastoma. Cancers (Basel) 11, 1406 (2019).","journal-title":"Cancers (Basel)"},{"key":"81733_CR4","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1126\/science.6248960","volume":"209","author":"BB Knowles","year":"1980","unstructured":"Knowles, B. B., Howe, C. C. & Aden, D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209, 497\u2013499 (1980).","journal-title":"Science"},{"key":"81733_CR5","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1096\/fasebj.4.2.2153592","volume":"4","author":"NB Javitt","year":"1990","unstructured":"Javitt, N. B. Hep G2 cells as a resource for metabolic studies: Lipoprotein, cholesterol, and bile acids. FASEB J. 4, 161\u2013168 (1990).","journal-title":"FASEB J."},{"key":"81733_CR6","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1016\/j.humpath.2009.07.003","volume":"40","author":"D Lopez-Terrada","year":"2009","unstructured":"Lopez-Terrada, D., Cheung, S. W., Finegold, M. J. & Knowles, B. B. Hep G2 is a hepatoblastoma-derived cell line. Hum. Pathol. 40, 1512\u20131515 (2009).","journal-title":"Hum. Pathol."},{"key":"81733_CR7","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S1388-1981(02)00365-7","volume":"1631","author":"SY Morita","year":"2003","unstructured":"Morita, S. Y. et al. Effects of sphingomyelin on apolipoprotein E- and lipoprotein lipase-mediated cell uptake of lipid particles. Biochim. Biophys. Acta 1631, 169\u2013176 (2003).","journal-title":"Biochim. Biophys. Acta"},{"key":"81733_CR8","doi-asserted-by":"publisher","first-page":"24355","DOI":"10.1074\/jbc.M402035200","volume":"279","author":"SY Morita","year":"2004","unstructured":"Morita, S. Y. et al. Ceramide in lipid particles enhances heparan sulfate proteoglycan and low density lipoprotein receptor-related protein-mediated uptake by macrophages. J. Biol. Chem. 279, 24355\u201324361 (2004).","journal-title":"J. Biol. Chem."},{"key":"81733_CR9","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1194\/jlr.M400132-JLR200","volume":"45","author":"J Shoda","year":"2004","unstructured":"Shoda, J. et al. Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARalpha-mediated redistribution of ABCB4. J. Lipid Res. 45, 1813\u20131825 (2004).","journal-title":"J. Lipid Res."},{"key":"81733_CR10","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/ncb1111","volume":"6","author":"T Ide","year":"2004","unstructured":"Ide, T. et al. SREBPs suppress IRS-2-mediated insulin signalling in the liver. Nat. Cell Biol. 6, 351\u2013357 (2004).","journal-title":"Nat. Cell Biol."},{"key":"81733_CR11","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.jhep.2013.02.030","volume":"59","author":"Y Morita","year":"2013","unstructured":"Morita, Y. et al. Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression. J. Hepatol. 59, 292\u2013299 (2013).","journal-title":"J. Hepatol."},{"key":"81733_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1248\/bpb.b15-00716","volume":"39","author":"SY Morita","year":"2016","unstructured":"Morita, S. Y. Metabolism and modification of apolipoprotein B-containing lipoproteins involved in dyslipidemia and atherosclerosis. Biol. Pharm. Bull. 39, 1\u201324 (2016).","journal-title":"Biol. Pharm. Bull."},{"key":"81733_CR13","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/s41598-017-00476-2","volume":"7","author":"Y Ikeda","year":"2017","unstructured":"Ikeda, Y., Morita, S. Y. & Terada, T. Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts. Sci. Rep. 7, 306 (2017).","journal-title":"Sci. Rep."},{"key":"81733_CR14","doi-asserted-by":"publisher","first-page":"12989","DOI":"10.1038\/s41598-019-49367-8","volume":"9","author":"Q Huang","year":"2019","unstructured":"Huang, Q., Lei, H., Ding, L. & Wang, Y. Stimulated phospholipid synthesis is key for hepatitis B virus replications. Sci. Rep. 9, 12989 (2019).","journal-title":"Sci. Rep."},{"key":"81733_CR15","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1248\/cpb.c18-01029","volume":"67","author":"SY Morita","year":"2019","unstructured":"Morita, S. Y., Ikeda, Y., Tsuji, T. & Terada, T. Molecular mechanisms for protection of hepatocytes against bile salt cytotoxicity. Chem. Pharm. Bull. 67, 333\u2013340 (2019).","journal-title":"Chem. Pharm. Bull."},{"key":"81733_CR16","doi-asserted-by":"publisher","first-page":"12466","DOI":"10.1038\/srep12466","volume":"5","author":"K Saito","year":"2015","unstructured":"Saito, K. et al. Characterization of hepatic lipid profiles in a mouse model with nonalcoholic steatohepatitis and subsequent fibrosis. Sci. Rep. 5, 12466 (2015).","journal-title":"Sci. Rep."},{"key":"81733_CR17","doi-asserted-by":"publisher","first-page":"7776","DOI":"10.1038\/s41598-019-43240-4","volume":"9","author":"JO Marentette","year":"2019","unstructured":"Marentette, J. O. et al. Multi-omics analysis of liver infiltrating macrophages following ethanol consumption. Sci. Rep. 9, 7776 (2019).","journal-title":"Sci. Rep."},{"key":"81733_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ20071040","volume":"409","author":"I M\u00e9rida","year":"2008","unstructured":"M\u00e9rida, I., Avila-Flores, A. & Merino, E. Diacylglycerol kinases: At the hub of cell signalling. Biochem. J. 409, 1\u201318 (2008).","journal-title":"Biochem. J."},{"key":"81733_CR19","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.bbalip.2009.02.009","volume":"1791","author":"DA Foster","year":"2009","unstructured":"Foster, D. A. Phosphatidic acid signaling to mTOR: Signals for the survival of human cancer cells. Biochim. Biophys. Acta 1791, 949\u2013955 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"81733_CR20","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.chemphyslip.2011.06.007","volume":"164","author":"M Scherer","year":"2011","unstructured":"Scherer, M. & Schmitz, G. Metabolism, function and mass spectrometric analysis of bis(monoacylglycero)phosphate and cardiolipin. Chem. Phys. Lipids 164, 556\u2013562 (2011).","journal-title":"Chem. Phys. Lipids"},{"key":"81733_CR21","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1152\/physrev.00028.2012","volume":"93","author":"T Balla","year":"2013","unstructured":"Balla, T. Phosphoinositides: Tiny lipids with giant impact on cell regulation. Physiol. Rev. 93, 1019\u20131137 (2013).","journal-title":"Physiol. Rev."},{"key":"81733_CR22","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.4161\/auto.24135","volume":"9","author":"J Zhu","year":"2013","unstructured":"Zhu, J., Wang, K. Z. & Chu, C. T. After the banquet: Mitochondrial biogenesis, mitophagy, and cell survival. Autophagy 9, 1663\u20131676 (2013).","journal-title":"Autophagy"},{"key":"81733_CR23","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.tcb.2015.08.003","volume":"25","author":"K Segawa","year":"2015","unstructured":"Segawa, K. & Nagata, S. An apoptotic \u2018eat me\u2019\u2019 signal: Phosphatidylserine exposure\u2019. Trends Cell Biol. 25, 639\u2013650 (2015).","journal-title":"Trends Cell Biol."},{"key":"81733_CR24","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.3390\/ijms21031032","volume":"21","author":"SY Morita","year":"2020","unstructured":"Morita, S. Y., Tsuji, T. & Terada, T. Protocols for enzymatic fluorometric assays to quantify phospholipid classes. Int. J. Mol. Sci. 21, 1032 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"81733_CR25","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.plipres.2010.05.002","volume":"49","author":"PJ Quinn","year":"2010","unstructured":"Quinn, P. J. A lipid matrix model of membrane raft structure. Prog. Lipid Res. 49, 390\u2013406 (2010).","journal-title":"Prog. Lipid Res."},{"key":"81733_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/tra.12230","volume":"16","author":"JE Vance","year":"2015","unstructured":"Vance, J. E. Phospholipid synthesis and transport in mammalian cells. Traffic (Copenhagen, Denmark) 16, 1\u201318 (2015).","journal-title":"Traffic (Copenhagen, Denmark)"},{"key":"81733_CR27","doi-asserted-by":"publisher","first-page":"6370","DOI":"10.1016\/S0021-9258(18)38127-4","volume":"266","author":"O Kuge","year":"1991","unstructured":"Kuge, O., Nishijima, M. & Akamatsu, Y. A cloned gene encoding phosphatidylserine decarboxylase complements the phosphatidylserine biosynthetic defect of a Chinese hamster ovary cell mutant. J. Biol. Chem. 266, 6370\u20136376 (1991).","journal-title":"J. Biol. Chem."},{"key":"81733_CR28","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1042\/BJ20081597","volume":"418","author":"S Tomohiro","year":"2009","unstructured":"Tomohiro, S., Kawaguti, A., Kawabe, Y., Kitada, S. & Kuge, O. Purification and characterization of human phosphatidylserine synthases 1 and 2. Biochem. J. 418, 421\u2013429 (2009).","journal-title":"Biochem. J."},{"key":"81733_CR29","first-page":"789","volume":"1","author":"DA Foster","year":"2003","unstructured":"Foster, D. A. & Xu, L. Phospholipase D in cell proliferation and cancer. Mol. Cancer Res. 1, 789\u2013800 (2003).","journal-title":"Mol. Cancer Res."},{"key":"81733_CR30","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1194\/jlr.R083964","volume":"59","author":"AL Egea-Jimenez","year":"2018","unstructured":"Egea-Jimenez, A. L. & Zimmermann, P. Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles. J. Lipid Res. 59, 1554\u20131560 (2018).","journal-title":"J. Lipid Res."},{"key":"81733_CR31","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.devcel.2011.09.005","volume":"21","author":"YJ Kim","year":"2011","unstructured":"Kim, Y. J., Guzman-Hernandez, M. L. & Balla, T. A highly dynamic ER-derived phosphatidylinositol-synthesizing organelle supplies phosphoinositides to cellular membranes. Dev. Cell 21, 813\u2013824 (2011).","journal-title":"Dev. Cell"},{"key":"81733_CR32","doi-asserted-by":"publisher","first-page":"7358","DOI":"10.1021\/bi501250m","volume":"53","author":"K D'Souza","year":"2014","unstructured":"D\u2019Souza, K., Kim, Y. J., Balla, T. & Epand, R. M. Distinct properties of the two isoforms of CDP-diacylglycerol synthase. Biochemistry 53, 7358\u20137367 (2014).","journal-title":"Biochemistry"},{"key":"81733_CR33","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S0005-2760(97)00119-7","volume":"1348","author":"M Schlame","year":"1997","unstructured":"Schlame, M. & Hostetler, K. Y. Cardiolipin synthase from mammalian mitochondria. Biochim. Biophys. Acta 1348, 207\u2013213 (1997).","journal-title":"Biochim. Biophys. Acta"},{"key":"81733_CR34","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1074\/jbc.274.3.1828","volume":"274","author":"K Kawasaki","year":"1999","unstructured":"Kawasaki, K. et al. Isolation of a Chinese hamster ovary (CHO) cDNA encoding phosphatidylglycerophosphate (PGP) synthase, expression of which corrects the mitochondrial abnormalities of a PGP synthase-defective mutant of CHO-K1 cells. J. Biol. Chem. 274, 1828\u20131834 (1999).","journal-title":"J. Biol. Chem."},{"key":"81733_CR35","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.plipres.2013.07.002","volume":"52","author":"SE Horvath","year":"2013","unstructured":"Horvath, S. E. & Daum, G. Lipids of mitochondria. Prog. Lipid Res. 52, 590\u2013614 (2013).","journal-title":"Prog. Lipid Res."},{"key":"81733_CR36","doi-asserted-by":"publisher","first-page":"29421","DOI":"10.1074\/jbc.R600021200","volume":"281","author":"FG Tafesse","year":"2006","unstructured":"Tafesse, F. G., Ternes, P. & Holthuis, J. C. The multigenic sphingomyelin synthase family. J. Biol. Chem. 281, 29421\u201329425 (2006).","journal-title":"J. Biol. Chem."},{"issue":"Pt 2","key":"81733_CR37","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1042\/bj3360257","volume":"336","author":"MM Zegers","year":"1998","unstructured":"Zegers, M. M. & Hoekstra, D. Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells. Biochem. J. 336(Pt 2), 257\u2013269 (1998).","journal-title":"Biochem. J."},{"key":"81733_CR38","doi-asserted-by":"publisher","first-page":"4768","DOI":"10.1111\/j.1742-4658.2011.08377.x","volume":"278","author":"SY Morita","year":"2011","unstructured":"Morita, S. Y. et al. Effects of phosphatidylethanolamine N-methyltransferase on phospholipid composition, microvillus formation and bile salt resistance in LLC-PK1 cells. FEBS J. 278, 4768\u20134781 (2011).","journal-title":"FEBS J."},{"key":"81733_CR39","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1194\/jlr.D900014-JLR200","volume":"50","author":"SY Morita","year":"2009","unstructured":"Morita, S. Y., Ueda, K. & Kitagawa, S. Enzymatic measurement of phosphatidic acid in cultured cells. J. Lipid Res. 50, 1945\u20131952 (2009).","journal-title":"J. Lipid Res."},{"key":"81733_CR40","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1042\/BJ20100490","volume":"432","author":"SY Morita","year":"2010","unstructured":"Morita, S. Y., Takeuchi, A. & Kitagawa, S. Functional analysis of two isoforms of phosphatidylethanolamine N-methyltransferase. Biochem. J. 432, 387\u2013398 (2010).","journal-title":"Biochem. J."},{"key":"81733_CR41","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1194\/jlr.D021808","volume":"53","author":"SY Morita","year":"2012","unstructured":"Morita, S. Y. et al. Enzymatic measurement of phosphatidylserine in cultured cells. J. Lipid Res. 53, 325\u2013330 (2012).","journal-title":"J. Lipid Res."},{"key":"81733_CR42","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.chemphyslip.2012.06.003","volume":"165","author":"SY Morita","year":"2012","unstructured":"Morita, S. Y., Soda, K., Teraoka, R., Kitagawa, S. & Terada, T. Specific and sensitive enzymatic measurement of sphingomyelin in cultured cells. Chem. Phys. Lipids 165, 571\u2013576 (2012).","journal-title":"Chem. Phys. Lipids"},{"key":"81733_CR43","doi-asserted-by":"publisher","first-page":"11737","DOI":"10.1038\/srep11737","volume":"5","author":"SY Morita","year":"2015","unstructured":"Morita, S. Y. & Terada, T. Enzymatic measurement of phosphatidylglycerol and cardiolipin in cultured cells and mitochondria. Sci. Rep. 5, 11737 (2015).","journal-title":"Sci. Rep."},{"key":"81733_CR44","doi-asserted-by":"publisher","first-page":"8607","DOI":"10.1038\/s41598-019-45185-0","volume":"9","author":"T Tsuji","year":"2019","unstructured":"Tsuji, T., Morita, S. Y., Ikeda, Y. & Terada, T. Enzymatic fluorometric assays for quantifying all major phospholipid classes in cells and intracellular organelles. Sci. Rep. 9, 8607 (2019).","journal-title":"Sci. Rep."},{"key":"81733_CR45","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1128\/iai.30.2.607-611.1980","volume":"30","author":"RJ Daemer","year":"1980","unstructured":"Daemer, R. J. et al. PLC\/PRF\/5 (Alexander) hepatoma cell line: Further characterization and studies of infectivity. Infect. Immun. 30, 607\u2013611 (1980).","journal-title":"Infect. Immun."},{"key":"81733_CR46","first-page":"706","volume":"9","author":"C Zhao","year":"2007","unstructured":"Zhao, C., Du, G., Skowronek, K., Frohman, M. A. & Bar-Sagi, D. Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nat. Cell Biol. 9, 706\u2013712 (2007).","journal-title":"Nat. Cell Biol."},{"key":"81733_CR47","doi-asserted-by":"publisher","first-page":"8472","DOI":"10.1074\/jbc.271.14.8472","volume":"271","author":"S Ghosh","year":"1996","unstructured":"Ghosh, S., Strum, J. C., Sciorra, V. A., Daniel, L. & Bell, R. M. Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-O-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells. J. Biol. Chem. 271, 8472\u20138480 (1996).","journal-title":"J. Biol. Chem."},{"key":"81733_CR48","doi-asserted-by":"publisher","first-page":"4251","DOI":"10.1073\/pnas.90.9.4251","volume":"90","author":"Z Zhao","year":"1993","unstructured":"Zhao, Z., Shen, S. H. & Fischer, E. H. Stimulation by phospholipids of a protein-tyrosine-phosphatase containing two src homology 2 domains. Proc. Natl. Acad. Sci. U. S. A. 90, 4251\u20134255 (1993).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"81733_CR49","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1083\/jcb.149.6.1215","volume":"149","author":"K Emoto","year":"2000","unstructured":"Emoto, K. & Umeda, M. An essential role for a membrane lipid in cytokinesis. Regulation of contractile ring disassembly by redistribution of phosphatidylethanolamine. J. Cell Biol. 149, 1215\u20131224 (2000).","journal-title":"J. Cell Biol."},{"key":"81733_CR50","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1007\/s00018-005-5195-z","volume":"62","author":"GM Jenkins","year":"2005","unstructured":"Jenkins, G. M. & Frohman, M. A. Phospholipase D: A lipid centric review. Cell. Mol. Life Sci. 62, 2305\u20132316 (2005).","journal-title":"Cell. Mol. Life Sci."},{"key":"81733_CR51","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.tibs.2011.09.003","volume":"37","author":"SM Claypool","year":"2012","unstructured":"Claypool, S. M. & Koehler, C. M. The complexity of cardiolipin in health and disease. Trends Biochem. Sci. 37, 32\u201341 (2012).","journal-title":"Trends Biochem. Sci."},{"key":"81733_CR52","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1194\/jlr.D400041-JLR200","volume":"46","author":"JL Macdonald","year":"2005","unstructured":"Macdonald, J. L. & Pike, L. J. A simplified method for the preparation of detergent-free lipid rafts. J. Lipid Res. 46, 1061\u20131067 (2005).","journal-title":"J. Lipid Res."},{"key":"81733_CR53","doi-asserted-by":"publisher","first-page":"266","DOI":"10.3389\/fonc.2016.00266","volume":"6","author":"M Cheng","year":"2016","unstructured":"Cheng, M., Bhujwalla, Z. M. & Glunde, K. Targeting phospholipid metabolism in cancer. Front. Oncol. 6, 266 (2016).","journal-title":"Front. Oncol."},{"key":"81733_CR54","doi-asserted-by":"publisher","first-page":"6230","DOI":"10.1074\/jbc.R117.000582","volume":"293","author":"Y Yang","year":"2018","unstructured":"Yang, Y., Lee, M. & Fairn, G. D. Phospholipid subcellular localization and dynamics. J. Biol. Chem. 293, 6230\u20136240 (2018).","journal-title":"J. Biol. Chem."},{"key":"81733_CR55","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1042\/bj20040095","volume":"380","author":"E Hutter","year":"2004","unstructured":"Hutter, E. et al. Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem. J. 380, 919\u2013928 (2004).","journal-title":"Biochem. J."},{"key":"81733_CR56","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1083\/jcb.91.2.392","volume":"91","author":"S Goldstein","year":"1981","unstructured":"Goldstein, S. & Korczack, L. B. Status of mitochondria in living human fibroblasts during growth and senescence in vitro: Use of the laser dye rhodamine 123. J. Cell Biol. 91, 392\u2013398 (1981).","journal-title":"J. Cell Biol."},{"key":"81733_CR57","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1016\/j.bbamem.2017.03.013","volume":"1859","author":"N Ikon","year":"2017","unstructured":"Ikon, N. & Ryan, R. O. Cardiolipin and mitochondrial cristae organization. Biochim. Biophys. Acta 1859, 1156\u20131163 (2017).","journal-title":"Biochim. Biophys. Acta"},{"key":"81733_CR58","doi-asserted-by":"publisher","first-page":"40032","DOI":"10.1074\/jbc.M506510200","volume":"280","author":"R Steenbergen","year":"2005","unstructured":"Steenbergen, R. et al. Disruption of the phosphatidylserine decarboxylase gene in mice causes embryonic lethality and mitochondrial defects. J. Biol. Chem. 280, 40032\u201340040 (2005).","journal-title":"J. Biol. Chem."},{"key":"81733_CR59","doi-asserted-by":"publisher","first-page":"4158","DOI":"10.1074\/jbc.M112.434183","volume":"288","author":"G Tasseva","year":"2013","unstructured":"Tasseva, G. et al. Phosphatidylethanolamine deficiency in Mammalian mitochondria impairs oxidative phosphorylation and alters mitochondrial morphology. J. Biol. Chem. 288, 4158\u20134173 (2013).","journal-title":"J. Biol. Chem."},{"key":"81733_CR60","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1126\/science.aab1370","volume":"349","author":"J Chung","year":"2015","unstructured":"Chung, J. et al. INTRACELLULAR TRANSPORT. PI4P\/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts. Science 349, 428\u2013432 (2015).","journal-title":"Science"},{"key":"81733_CR61","doi-asserted-by":"publisher","first-page":"800","DOI":"10.15252\/embr.201541108","volume":"17","author":"R Galmes","year":"2016","unstructured":"Galmes, R. et al. ORP5\/ORP8 localize to endoplasmic reticulum-mitochondria contacts and are involved in mitochondrial function. EMBO Rep. 17, 800\u2013810 (2016).","journal-title":"EMBO Rep."},{"key":"81733_CR62","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.abb.2010.06.004","volume":"501","author":"R Sato","year":"2010","unstructured":"Sato, R. Sterol metabolism and SREBP activation. Arch. Biochem. Biophys. 501, 177\u2013181 (2010).","journal-title":"Arch. Biochem. Biophys."},{"key":"81733_CR63","doi-asserted-by":"publisher","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","volume":"64","author":"CL Andersen","year":"2004","unstructured":"Andersen, C. L., Jensen, J. L. & Orntoft, T. F. Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 64, 5245\u20135250 (2004).","journal-title":"Cancer Res."},{"key":"81733_CR64","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","volume":"26","author":"MW Pfaffl","year":"2004","unstructured":"Pfaffl, M. W., Tichopad, A., Prgomet, C. & Neuvians, T. P. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper\u2013Excel-based tool using pair-wise correlations. Biotechnol. Lett. 26, 509\u2013515 (2004).","journal-title":"Biotechnol. Lett."},{"key":"81733_CR65","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen, T. D. & Livak, K. J. Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 3, 1101\u20131108 (2008).","journal-title":"Nat. Protoc."},{"key":"81733_CR66","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1074\/jbc.271.1.478","volume":"271","author":"JP Humbert","year":"1996","unstructured":"Humbert, J. P., Matter, N., Artault, J. C., Koppler, P. & Malviya, A. N. Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane vindicating regulation of nuclear calcium signaling by inositol 1,4,5-trisphosphate. Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes. J. Biol. Chem. 271, 478\u2013485 (1996).","journal-title":"J. Biol. Chem."},{"key":"81733_CR67","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1038\/nprot.2009.151","volume":"4","author":"MR Wieckowski","year":"2009","unstructured":"Wieckowski, M. R., Giorgi, C., Lebiedzinska, M., Duszynski, J. & Pinton, P. Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells. Nat. Protoc. 4, 1582\u20131590 (2009).","journal-title":"Nat. Protoc."},{"key":"81733_CR68","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","volume":"226","author":"J Folch","year":"1957","unstructured":"Folch, J., Lees, M. & Sloane Stanley, G. H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497\u2013509 (1957).","journal-title":"J. Biol. Chem."},{"key":"81733_CR69","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1194\/jlr.D094516","volume":"60","author":"H Takeda","year":"2019","unstructured":"Takeda, H., Takahashi, M., Hara, T., Izumi, Y. & Bamba, T. Improved quantitation of lipid classes using supercritical fluid chromatography with a charged aerosol detector. J. Lipid Res. 60, 1465\u20131474 (2019).","journal-title":"J. Lipid Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-81733-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-81733-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-81733-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T02:49:44Z","timestamp":1670035784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-81733-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["81733"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-81733-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,1]]},"assertion":[{"value":"9 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2731"}}