{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:16:00Z","timestamp":1789805760580,"version":"4.0.1"},"reference-count":46,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cellular energy homeostasis is tightly regulated by mitochondrial function and substrate availability. Vitamin C is a redox-active molecule with emerging roles in cellular metabolism; however, the metabolic impacts of structurally distinct vitamin C derivatives remain incompletely defined. In this study, we systematically compared\n                    <jats:sc>l<\/jats:sc>\n                    -ascorbic acid, dehydroascorbic acid, 6-O-palmitoyl-\n                    <jats:sc>l<\/jats:sc>\n                    -ascorbate, and mineral ascorbates (calcium, magnesium, sodium, and potassium salts) across multiple mammalian cell types. Cells were exposed to concentrations ranging from 60 to 500\u202f\u00b5M, encompassing physiologically and pharmacologically relevant levels. The vitamin C derivatives induced cell type- and concentration-dependent modulation of intracellular ATP levels. Notably, HepG2 and renal epithelial cells exhibited robust ATP increases, whereas fibroblasts, myocytes, microglia, and skeletal muscle models displayed variable responses depending on the derivative and dose. Moreover, in skeletal muscle cells, co-treatment of standard\n                    <jats:sc>l<\/jats:sc>\n                    -ascorbic acid with select fatty acids did not yield additive bioenergetic effects, suggesting a localized, substrate-specific plateau or shared regulatory step in this specific cell model. Exposure to\n                    <jats:sc>l<\/jats:sc>\n                    -ascorbic acid induced selective increases in COX-1 without changes in SDH-A, consistent with rapid functional modulation of mitochondrial activity in myocytes and microglial cells only. Collectively, these findings demonstrate that vitamin C derivatives modulate cellular ATP levels within existing metabolic networks in a context-dependent manner, consistent with the modulation of mitochondrial-associated energy metabolism.\n                  <\/jats:p>","DOI":"10.1515\/biol-2025-1383","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:57:07Z","timestamp":1789804627000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparative analysis of vitamin C derivatives on ATP homeostasis across diverse cell types"],"prefix":"10.1515","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-2941","authenticated-orcid":false,"given":"Anna","family":"Goc","sequence":"first","affiliation":[{"name":"Dr. Rath Research Institute , 5941 Optical Ct., 95138 , San Jose , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Sumera","sequence":"additional","affiliation":[{"name":"Dr. Rath Research Institute , 5941 Optical Ct., 95138 , San Jose , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Niedzwiecki","sequence":"additional","affiliation":[{"name":"Dr. Rath Research Institute , 5941 Optical Ct., 95138 , San Jose , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026091907570205935_j_biol-2025-1383_ref_001","unstructured":"Mitchell, P. Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biol Rev 1961;36:1\u201324."},{"key":"2026091907570205935_j_biol-2025-1383_ref_002","unstructured":"Nicholls, DG, Ferguson, SJ. Bioenergetics 4. London: Academic Press; 2013."},{"key":"2026091907570205935_j_biol-2025-1383_ref_003","doi-asserted-by":"crossref","unstructured":"Spinelli, JB, Haigis, MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol 2018;20:745\u201354. https:\/\/doi.org\/10.1038\/s41556-018-0124-1.","DOI":"10.1038\/s41556-018-0124-1"},{"key":"2026091907570205935_j_biol-2025-1383_ref_004","doi-asserted-by":"crossref","unstructured":"Murphy, MP. How mitochondria produce reactive oxygen species. Biochem J 2009;417:1\u201313. https:\/\/doi.org\/10.1042\/bj20081386.","DOI":"10.1042\/BJ20081386"},{"key":"2026091907570205935_j_biol-2025-1383_ref_005","doi-asserted-by":"crossref","unstructured":"Wallace, DC. Mitochondrial genetic medicine. Nat Genet 2018;50:1642\u20139. https:\/\/doi.org\/10.1038\/s41588-018-0264-z.","DOI":"10.1038\/s41588-018-0264-z"},{"key":"2026091907570205935_j_biol-2025-1383_ref_006","doi-asserted-by":"crossref","unstructured":"Nunnari, J, Suomalainen, A. Mitochondria: in sickness and in health. Cell 2012;148:1145\u201359. https:\/\/doi.org\/10.1016\/j.cell.2012.02.035.","DOI":"10.1016\/j.cell.2012.02.035"},{"key":"2026091907570205935_j_biol-2025-1383_ref_007","doi-asserted-by":"crossref","unstructured":"Hardie, DG. AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole body levels. Annu Rev Nutr 2014;34:31\u201355. https:\/\/doi.org\/10.1146\/annurev-nutr-071812-161148.","DOI":"10.1146\/annurev-nutr-071812-161148"},{"key":"2026091907570205935_j_biol-2025-1383_ref_008","doi-asserted-by":"crossref","unstructured":"Scarpulla, RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family. Biochim Biophys Acta 2011;1813:1269\u201378. https:\/\/doi.org\/10.1016\/j.bbamcr.2010.09.019.","DOI":"10.1016\/j.bbamcr.2010.09.019"},{"key":"2026091907570205935_j_biol-2025-1383_ref_009","doi-asserted-by":"crossref","unstructured":"Liang, H, Ward, WF. PGC-1\u03b1: a key regulator of energy metabolism. Physiology 2006;21:396\u2013405.","DOI":"10.1152\/advan.00052.2006"},{"key":"2026091907570205935_j_biol-2025-1383_ref_010","doi-asserted-by":"crossref","unstructured":"Sagan, KC, Carcamo, JM, Golde, DW. Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury. FASEB J 2005;19:1657\u201367.","DOI":"10.1096\/fj.05-4107com"},{"key":"2026091907570205935_j_biol-2025-1383_ref_011","doi-asserted-by":"crossref","unstructured":"Carr, AC, Maggini, S. Vitamin C and immune function. Nutrients 2017;9:1211. https:\/\/doi.org\/10.3390\/nu9111211.","DOI":"10.3390\/nu9111211"},{"key":"2026091907570205935_j_biol-2025-1383_ref_012","doi-asserted-by":"crossref","unstructured":"Duarte, TL, Lunec, J. When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C. Free Radic Res 2005;39:671\u201386.","DOI":"10.1080\/10715760500104025"},{"key":"2026091907570205935_j_biol-2025-1383_ref_013","doi-asserted-by":"crossref","unstructured":"Yun, J, Mullarky, E, Lu, C, Bosch, KN, Kavalier, A, Rivera, K, et al.. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 2015;350:1391\u20136. https:\/\/doi.org\/10.1126\/science.aaa5004.","DOI":"10.1126\/science.aaa5004"},{"key":"2026091907570205935_j_biol-2025-1383_ref_014","doi-asserted-by":"crossref","unstructured":"Aguilera, O, Mu\u00f1oz-Sagastibelza, M, Torrej\u00f3n, B, Borrero-Palacios, A, Del Puerto-Nevado, L, Martinez-Useros, J, et al.. Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer. Oncotarget 2016;7:47954\u201365. https:\/\/doi.org\/10.18632\/oncotarget.10087.","DOI":"10.18632\/oncotarget.10087"},{"key":"2026091907570205935_j_biol-2025-1383_ref_015","doi-asserted-by":"crossref","unstructured":"Blaschke, K, Ebata, KT, Karimi, MM, Zepeda-Martinez, JA, Goyal, P, Mahapatra, S, et al.. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature 2013;500:222\u20136. https:\/\/doi.org\/10.1038\/nature12362.","DOI":"10.1038\/nature12362"},{"key":"2026091907570205935_j_biol-2025-1383_ref_016","doi-asserted-by":"crossref","unstructured":"Zhitkovich, A. Ascorbate: antioxidant and biochemical activities and their importance for in\u00a0vitro models. Mol Aspect Med 2021;82:101007.","DOI":"10.1007\/s00204-021-03167-0"},{"key":"2026091907570205935_j_biol-2025-1383_ref_017","doi-asserted-by":"crossref","unstructured":"Kleszczewski, T, Kleszczewska, E. Flow injection spectrophotometric determination of L-ascorbic acid (vitamin C) in tissues. J\u00a0Pharm Biomed Anal 2002;29:755\u20139. https:\/\/doi.org\/10.1016\/s0731-7085(02)00127-9.","DOI":"10.1016\/S0731-7085(02)00127-9"},{"key":"2026091907570205935_j_biol-2025-1383_ref_018","unstructured":"Pande, RE, Sabnis, SS, Srinivas, NR. Ascorbyl palmitate: a comprehensive review on its characteristics, biological activities, and synthesis methods. Bioproc Biosyst Eng 2024;47:1201\u201315."},{"key":"2026091907570205935_j_biol-2025-1383_ref_019","doi-asserted-by":"crossref","unstructured":"Smart, RC, Crawford, J. Vitamin C derivative ascorbyl palmitate promotes ultraviolet-B-induced lipid peroxidation and cytotoxicity in keratinocytes. J\u00a0Invest Dermatol 2002;119:1103\u20138.","DOI":"10.1046\/j.1523-1747.2002.19521.x"},{"key":"2026091907570205935_j_biol-2025-1383_ref_020","doi-asserted-by":"crossref","unstructured":"Castro, M, Low, M, Salazar-Atenas, L, Nualart, F. Vitamin C in health and disease: its role in the metabolism of cells and redox state in the brain. Front Physiol 2015;6:397.","DOI":"10.3389\/fphys.2015.00397"},{"key":"2026091907570205935_j_biol-2025-1383_ref_021","doi-asserted-by":"crossref","unstructured":"Levine, M, Padayatty, SJ, Corpe, C. Chemical transport knockout for oxidized vitamin C (dehydroascorbic acid) reveals its functions in\u00a0vivo. EBioMedicine 2017;23:125\u201335.","DOI":"10.1016\/j.ebiom.2017.08.017"},{"key":"2026091907570205935_j_biol-2025-1383_ref_022","doi-asserted-by":"crossref","unstructured":"Houten, SM, Wanders, RJA. A general introduction to fatty acid oxidation. J\u00a0Inherit Metab Dis 2010;33:469\u201377.","DOI":"10.1007\/s10545-010-9061-2"},{"key":"2026091907570205935_j_biol-2025-1383_ref_023","doi-asserted-by":"crossref","unstructured":"McGarry, JD, Brown, NF. The mitochondrial carnitine palmitoyltransferase system. Eur J Biochem 1997;244:1\u201314.","DOI":"10.1111\/j.1432-1033.1997.00001.x"},{"key":"2026091907570205935_j_biol-2025-1383_ref_024","doi-asserted-by":"crossref","unstructured":"Finck, BN, Kelly, DP. PGC-1 coactivators and the regulation of cardiac energy metabolism. J\u00a0Clin Investig 2006;116:615\u201322.","DOI":"10.1172\/JCI27794"},{"key":"2026091907570205935_j_biol-2025-1383_ref_025","doi-asserted-by":"crossref","unstructured":"Lange, LG, Sobel, BE. Mitochondrial dysfunction induced by fatty acid ethyl esters, myocardial metabolites of ethanol. J\u00a0Clin Investig 1983;72:724\u201331. https:\/\/doi.org\/10.1172\/jci111022.","DOI":"10.1172\/JCI111022"},{"key":"2026091907570205935_j_biol-2025-1383_ref_026","doi-asserted-by":"crossref","unstructured":"Lodhi, IJ, Semenkovich, CF. Peroxisomes: a nexus for lipid metabolism and cellular signaling. Cell Metab 2014;19:380\u201392. https:\/\/doi.org\/10.1016\/j.cmet.2014.01.002.","DOI":"10.1016\/j.cmet.2014.01.002"},{"key":"2026091907570205935_j_biol-2025-1383_ref_027","doi-asserted-by":"crossref","unstructured":"Locasale, JW, Cantley, LC. Metabolic flux and the regulation of Mammalian cell growth. Cell Metab 2011;14:443\u201351. https:\/\/doi.org\/10.1016\/j.cmet.2011.07.014.","DOI":"10.1016\/j.cmet.2011.07.014"},{"key":"2026091907570205935_j_biol-2025-1383_ref_028","unstructured":"Hue, L, Taegtmeyer, H. The Randle cycle revisited. FASEB J 2009;23:1964\u201373."},{"key":"2026091907570205935_j_biol-2025-1383_ref_029","unstructured":"Berg, JM, Tymoczko, JL, Gatto, GJ, Stryer, L. Biochemistry, 8th ed. New York: W. H. Freeman; 2015."},{"key":"2026091907570205935_j_biol-2025-1383_ref_030","doi-asserted-by":"crossref","unstructured":"Lopaschuk, GD, Saddik, M. The relative contribution of glucose and fatty acids to ATP production in hearts reperfused following ischemia. Mol Cell Biochem 1992;116:111\u201316.","DOI":"10.1007\/978-1-4615-3514-0_16"},{"key":"2026091907570205935_j_biol-2025-1383_ref_031","doi-asserted-by":"crossref","unstructured":"Guerra, IMS, Ferreira, HB, Melo, T, Rocha, H, Moreira, S, Diogo, L, et al.. Mitochondrial fatty acid \u03b2-oxidation disorders: from disease to lipidomic studies\u2014A critical review. Int J Mol Sci 2022;23:13933. https:\/\/doi.org\/10.3390\/ijms232213933.","DOI":"10.3390\/ijms232213933"},{"key":"2026091907570205935_j_biol-2025-1383_ref_032","doi-asserted-by":"crossref","unstructured":"Dikalov, S, Panov, A, Dikalova, A. Critical role of mitochondrial fatty acid metabolism in normal cell function and pathological conditions. Int J Mol Sci 2024;25:6498. https:\/\/doi.org\/10.3390\/ijms25126498.","DOI":"10.3390\/ijms25126498"},{"key":"2026091907570205935_j_biol-2025-1383_ref_033","doi-asserted-by":"crossref","unstructured":"Chen, D, Li, X, Zhang, L, Zhu, M, Gao, L. A high-fat diet impairs mitochondrial biogenesis, mitochondrial dynamics, and the respiratory chain complex in rat myocardial tissues. J\u00a0Cell Biochem 2018;119:9602. https:\/\/doi.org\/10.1002\/jcb.27068.","DOI":"10.1002\/jcb.27068"},{"key":"2026091907570205935_j_biol-2025-1383_ref_034","doi-asserted-by":"crossref","unstructured":"Ramachandra, CJA, Mehta, A, Wong, P, Mai Ja, KPM, Fritsche-Danielson, R, Bhat, RV, et al.. Fatty acid metabolism driven mitochondrial bioenergetics promotes advanced developmental phenotypes in human induced pluripotent stem cell derived cardiomyocytes. Int J Cardiol 2018;272:288\u201397. https:\/\/doi.org\/10.1016\/j.ijcard.2018.08.069.","DOI":"10.1016\/j.ijcard.2018.08.069"},{"key":"2026091907570205935_j_biol-2025-1383_ref_035","doi-asserted-by":"crossref","unstructured":"Toleikis, A, Trumbeckaite, S, Liobikas, J, Pauziene, N, Kursvietiene, L, Kopustinskiene, DM. Fatty acid oxidation and mitochondrial morphology changes as key modulators of the affinity for ADP in rat heart mitochondria. Cells 2020;9:340. https:\/\/doi.org\/10.3390\/cells9020340.","DOI":"10.3390\/cells9020340"},{"key":"2026091907570205935_j_biol-2025-1383_ref_036","doi-asserted-by":"crossref","unstructured":"Allegra, A, Pioggia, G, Gangemi, S. High-dose vitamin C: preclinical evidence for tailoring treatment in cancer patients. Cancers (Basel) 2021;13:1428.","DOI":"10.3390\/cancers13061428"},{"key":"2026091907570205935_j_biol-2025-1383_ref_037","doi-asserted-by":"crossref","unstructured":"Padayatty, SJ, Sun, H, Wang, Y, Riordan, HD, Hewitt, SM, Katz, A, et al.. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 2004;140:533\u20137. https:\/\/doi.org\/10.7326\/0003-4819-140-7-200404060-00010.","DOI":"10.7326\/0003-4819-140-7-200404060-00010"},{"key":"2026091907570205935_j_biol-2025-1383_ref_038","doi-asserted-by":"crossref","unstructured":"Pawlowska, E, Szczepanska, J, Blasiak, J. Pro- and antioxidant effects of vitamin C in cancer in correspondence to its dietary and pharmacological concentrations. Oxid Med Cell Longev 2019;2019:7286737\u201318. https:\/\/doi.org\/10.1155\/2019\/7286737.","DOI":"10.1155\/2019\/7286737"},{"key":"2026091907570205935_j_biol-2025-1383_ref_039","doi-asserted-by":"crossref","unstructured":"Roa, FJ, Pe\u00f1a, E, Gatica, M, Escobar-Acu\u00f1a, K, Saavedra, P, Maldonado, M, et al.. Therapeutic use of vitamin C in cancer: physiological considerations. Front Pharmacol 2020;11:211. https:\/\/doi.org\/10.3389\/fphar.2020.00211.","DOI":"10.3389\/fphar.2020.00211"},{"key":"2026091907570205935_j_biol-2025-1383_ref_040","doi-asserted-by":"crossref","unstructured":"Uetaki, M, Tabata, S, Nakasuka, F, Soga, T, Tomita, M. Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress. Sci Rep 2015;5:13896. https:\/\/doi.org\/10.1038\/srep13896.","DOI":"10.1038\/srep13896"},{"key":"2026091907570205935_j_biol-2025-1383_ref_041","doi-asserted-by":"crossref","unstructured":"Brand, MD, Nicholls, DG. Assessing mitochondrial dysfunction in cells. Biochem J 2011;435:297\u2013312.","DOI":"10.1042\/BJ20110162"},{"key":"2026091907570205935_j_biol-2025-1383_ref_042","doi-asserted-by":"crossref","unstructured":"Killilea, DW, Killilea, AN. Mineral requirements for mitochondrial function: a connection to redox balance and cellular differentiation. Free Radic Biol Med 2022;182:182\u201391. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2022.02.022.","DOI":"10.1016\/j.freeradbiomed.2022.02.022"},{"key":"2026091907570205935_j_biol-2025-1383_ref_043","doi-asserted-by":"crossref","unstructured":"Mu, X, Evans, TD, Zhang, F. ATP biosensor reveals microbial energetic dynamics and facilitates bioproduction. Nat Commun 2024;15:15299. https:\/\/doi.org\/10.1038\/s41467-024-49579-1.","DOI":"10.1038\/s41467-024-49579-1"},{"key":"2026091907570205935_j_biol-2025-1383_ref_044","doi-asserted-by":"crossref","unstructured":"Villagr\u00e1n, M, Ferreira, J, Martorell, M, Celis-Morales, C. The role of vitamin C in cancer prevention and therapy: a literature review. Antioxidants 2021;10:1894. https:\/\/doi.org\/10.3390\/antiox10121894.","DOI":"10.3390\/antiox10121894"},{"key":"2026091907570205935_j_biol-2025-1383_ref_045","doi-asserted-by":"crossref","unstructured":"Bedhiafi, T, Inchakalody, VP, Fernandes, Q, Uddin, S, Dermime, S. High-dose vitamin C for cancer therapy. Pharmaceuticals 2022;15:711.","DOI":"10.3390\/ph15060711"},{"key":"2026091907570205935_j_biol-2025-1383_ref_046","doi-asserted-by":"crossref","unstructured":"Jankowski, CSR, Rabinowitz, JD. Selenium modulates cancer cell response to pharmacologic ascorbate. Cancer Res 2022;82:3532\u201343. https:\/\/doi.org\/10.1158\/0008-5472.can-22-0408.","DOI":"10.1158\/0008-5472.CAN-22-0408"}],"container-title":["Open Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/biol-2025-1383\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/biol-2025-1383\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:57:17Z","timestamp":1789804637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/biol-2025-1383\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,1,23]]}},"alternative-id":["10.1515\/biol-2025-1383"],"URL":"https:\/\/doi.org\/10.1515\/biol-2025-1383","relation":{},"ISSN":["2391-5412"],"issn-type":[{"value":"2391-5412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]},"article-number":"20251383"}}