{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:55:59Z","timestamp":1789131359152,"version":"build-2803163510"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Hangzhou Medical Science and Technology Project","award":["A20230193"],"award-info":[{"award-number":["A20230193"]}]},{"name":"Zhejiang Province Medical Science and Technology Plan Project","award":["2024KY1359"],"award-info":[{"award-number":["2024KY1359"]}]},{"DOI":"10.13039\/501100005199","name":"Chinese Medicine Research Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2022ZB261"],"award-info":[{"award-number":["2022ZB261"]}],"id":[{"id":"10.13039\/501100005199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005199","name":"Chinese Medicine Research Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2025ZL100"],"award-info":[{"award-number":["2025ZL100"]}],"id":[{"id":"10.13039\/501100005199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005199","name":"Chinese Medicine Research Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2026ZL0583"],"award-info":[{"award-number":["2026ZL0583"]}],"id":[{"id":"10.13039\/501100005199","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hangzhou Red Cross Hospital Youth fund project","award":["HHQN2023002"],"award-info":[{"award-number":["HHQN2023002"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Human Cell"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ethambutol (EMB)-induced optic neuropathy (EON) is a clinical concern. Ferroptosis, involving iron and toxic reactive oxygen species (ROS), causes unique cell death, but its mechanism in EON is unclear. This study aims to explore the EON mechanisms. Wistar rats were used to establish an EON model by administering EMB at 50\u00a0mg\/kg daily for 8\u00a0weeks. Retinal ganglion cells (RGC-5 cells) were used for in vitro experiments. Histological staining, MTT assays, flow cytometry, western blot analysis, dual-luciferase reporter assay, chromatin immunoprecipitation, and high-throughput sequencing were conducted to investigate cell death modes and molecular changes. EMB treatment leads to significant cell loss and structural damage in RGCs of EON model, predominantly through ferroptosis. We confirm increased ROS levels, downregulation of SLC7A11 and GPX4, and decreased glutathione (GSH) levels, upregulation of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels in EMB-treated RGC-5 cells. Furthermore, sequencing data reveal that in RGC-5 cells treated with EMB, the differentially expressed genes (DEGs) primarily exhibited alterations in biological functions associated with metabolism, stress response, and apoptotic regulation. Specifically, EMB inhibits the expression of succinate dehydrogenase enzyme B (SDHB), thereby disrupting antioxidant defenses and facilitating ferroptosis. Moreover, Smad4 has been pinpointed as a pivotal transcription factor in regulating SDHB expression. Notably, its interaction with the promoter region of SDHB is inhibited by EMB. This study provides compelling evidence for the involvement of ferroptosis in EON and highlights SDHB and Smad4 as potential therapeutic targets for mitigating this adverse effect.<\/jats:p>","DOI":"10.1007\/s13577-025-01342-4","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:48:59Z","timestamp":1768974539000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ethambutol induces optic neuropathy through SDHB-mediated ferroptosis in retinal ganglion cells via Smad4 pathway"],"prefix":"10.1007","volume":"39","author":[{"given":"Qiushi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qibin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junli","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingneng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"1342_CR1","first-page":"910","volume":"38","author":"T Wang","year":"2016","unstructured":"Wang T, Jiao WW, Shen AD. Progress on mechanism of ethambutol resistance in Mycobacterium tuberculosis. Yi Chuan. 2016;38:910\u20137.","journal-title":"Yi Chuan"},{"key":"1342_CR2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.ijmm.2008.07.001","volume":"299","author":"S Srivastava","year":"2009","unstructured":"Srivastava S, Ayyagari A, Dhole TN, Nyati KK, Dwivedi SK. Emb nucleotide polymorphisms and the role of embB306 mutations in Mycobacterium tuberculosis resistance to ethambutol. Int J Med Microbiol. 2009;299:269\u201380.","journal-title":"Int J Med Microbiol"},{"key":"1342_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.754676","volume":"9","author":"XH Zhang","year":"2021","unstructured":"Zhang XH, Xie Y, Xu QG, et al. Mitochondrial mutations in ethambutol-induced optic neuropathy. Front Cell Dev Biol. 2021;9:754676.","journal-title":"Front Cell Dev Biol"},{"key":"1342_CR4","doi-asserted-by":"publisher","first-page":"261","DOI":"10.5588\/ijtld.15.0275","volume":"20","author":"HK Yang","year":"2016","unstructured":"Yang HK, Park MJ, Lee JH, Lee CT, Park JS, Hwang JM. Incidence of toxic optic neuropathy with low-dose ethambutol. Int J Tuberc Lung Dis. 2016;20:261\u20134.","journal-title":"Int J Tuberc Lung Dis"},{"key":"1342_CR5","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1097\/ICU.0000000000000416","volume":"28","author":"PD Chamberlain","year":"2017","unstructured":"Chamberlain PD, Sadaka A, Berry S, Lee AG. Ethambutol optic neuropathy. Curr Opin Ophthalmol. 2017;28:545\u201351.","journal-title":"Curr Opin Ophthalmol"},{"key":"1342_CR6","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1111\/aos.12515","volume":"93","author":"A Grzybowski","year":"2015","unstructured":"Grzybowski A, Z\u00fclsdorff M, Wilhelm H, Tonagel F. Toxic optic neuropathies: an updated review. Acta Ophthalmol. 2015;93:402\u201310.","journal-title":"Acta Ophthalmol"},{"key":"1342_CR7","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.kjms.2015.05.004","volume":"31","author":"SC Chen","year":"2015","unstructured":"Chen SC, Lin MC, Sheu SJ. Incidence and prognostic factor of ethambutol-related optic neuropathy: 10-year experience in southern Taiwan. Kaohsiung J Med Sci. 2015;31:358\u201362.","journal-title":"Kaohsiung J Med Sci"},{"key":"1342_CR8","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1097\/WNO.0b013e31818e3c6b","volume":"28","author":"EJ Lee","year":"2008","unstructured":"Lee EJ, Kim SJ, Choung HK, Kim JH, Yu YS. Incidence and clinical features of ethambutol-induced optic neuropathy in Korea. J Neuroophthalmol. 2008;28:269\u201377.","journal-title":"J Neuroophthalmol"},{"key":"1342_CR9","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1136\/bjophthalmol-2018-312063","volume":"103","author":"JY Lee","year":"2019","unstructured":"Lee JY, Han J, Seo JG, Park KA, Oh SY. Diagnostic value of ganglion cell-inner plexiform layer for early detection of ethambutol-induced optic neuropathy. Br J Ophthalmol. 2019;103:379\u201384.","journal-title":"Br J Ophthalmol"},{"key":"1342_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fopht.2023.1152215","volume":"3","author":"P Chaitanuwong","year":"2023","unstructured":"Chaitanuwong P, Srithawatpong S, Ruamviboonsuk P, Apinyawasisuk S, Watcharapanjamart A, Moss HE. Incidence, risk factors and ophthalmic clinical characteristic of ethambutol-induced optic neuropathy: 7-year experience. Front Ophthalmol. 2023;3:1152215.","journal-title":"Front Ophthalmol"},{"key":"1342_CR11","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1136\/bjo.2006.113118","volume":"91","author":"SJ Chai","year":"2007","unstructured":"Chai SJ, Foroozan R. Decreased retinal nerve fibre layer thickness detected by optical coherence tomography in patients with ethambutol-induced optic neuropathy. Br J Ophthalmol. 2007;91:895\u20137.","journal-title":"Br J Ophthalmol"},{"key":"1342_CR12","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1136\/bjophthalmol-2020-317742","volume":"106","author":"L Su","year":"2022","unstructured":"Su L, Li Q, Zhu L, et al. Characterisation of macular superficial vessel density alteration in preclinical ethambutol-induced optic neuropathy using optical coherence tomography angiography. Br J Ophthalmol. 2022;106:422\u20136.","journal-title":"Br J Ophthalmol"},{"key":"1342_CR13","doi-asserted-by":"publisher","first-page":"222","DOI":"10.3109\/15569527.2015.1077857","volume":"35","author":"E Cinici","year":"2016","unstructured":"Cinici E, Cetin N, Ahiskali I, et al. The effect of thiamine pyrophosphate on ethambutol-induced ocular toxicity. Cutan Ocul Toxicol. 2016;35:222\u20137.","journal-title":"Cutan Ocul Toxicol"},{"key":"1342_CR14","first-page":"977","volume":"8","author":"SP Huang","year":"2015","unstructured":"Huang SP, Chien JY, Tsai RK. Ethambutol induces impaired autophagic flux and apoptosis in the rat retina. Dis Model Mech. 2015;8:977\u201387.","journal-title":"Dis Model Mech"},{"key":"1342_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10101538","author":"B Sanz-Morello","year":"2021","unstructured":"Sanz-Morello B, Ahmadi H, Vohra R, et al. Oxidative stress in optic neuropathies. Antioxidants. 2021. https:\/\/doi.org\/10.3390\/antiox10101538.","journal-title":"Antioxidants"},{"key":"1342_CR16","doi-asserted-by":"publisher","first-page":"5712","DOI":"10.1167\/iovs.13-12085","volume":"54","author":"RR Krishnamoorthy","year":"2013","unstructured":"Krishnamoorthy RR, Clark AF, Daudt D, Vishwanatha JK, Yorio T. A forensic path to RGC-5 cell line identification: lessons learned. Invest Ophthalmol Vis Sci. 2013;54:5712\u20139.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1342_CR17","doi-asserted-by":"publisher","first-page":"4267","DOI":"10.1167\/iovs.09-3484","volume":"50","author":"NJ Van Bergen","year":"2009","unstructured":"Van Bergen NJ, Wood JP, Chidlow G, et al. Recharacterization of the RGC-5 retinal ganglion cell line. Invest Ophthalmol Vis Sci. 2009;50:4267\u201372.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1342_CR18","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1089\/jop.2022.0005","volume":"38","author":"S Nusanti","year":"2022","unstructured":"Nusanti S, Sari RI, Siregar NC, Sidik M. The effect of Citicoline on Ethambutol Optic Neuropathy: histopathology and immunohistochemistry analysis of retina ganglion cell damage level in rat model. J Ocul Pharmacol Ther. 2022;38:584\u20139.","journal-title":"J Ocul Pharmacol Ther"},{"key":"1342_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108111","volume":"26","author":"G Li","year":"2023","unstructured":"Li G, Luo Y, Zhang Q, et al. The RBPMS(CreERT2-tdTomato) mouse line for studying retinal and vascular relevant diseases. iScience. 2023;26:108111.","journal-title":"iScience"},{"key":"1342_CR20","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12886-021-01881-y","volume":"21","author":"WY Sheng","year":"2021","unstructured":"Sheng WY, Su LY, Ge W, Wu SQ, Zhu LW. Analysis of structural injury patterns in peripapillary retinal nerve fibre layer and retinal ganglion cell layer in ethambutol-induced optic neuropathy. BMC Ophthalmol. 2021;21:132.","journal-title":"BMC Ophthalmol"},{"key":"1342_CR21","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.canlet.2016.04.002","volume":"376","author":"DH Liang","year":"2016","unstructured":"Liang DH, Choi DS, Ensor JE, Kaipparettu BA, Bass BL, Chang JC. The autophagy inhibitor chloroquine targets cancer stem cells in triple negative breast cancer by inducing mitochondrial damage and impairing DNA break repair. Cancer Lett. 2016;376:249\u201358.","journal-title":"Cancer Lett"},{"key":"1342_CR22","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.freeradbiomed.2020.07.026","volume":"160","author":"T Bai","year":"2020","unstructured":"Bai T, Li M, Liu Y, Qiao Z, Wang Z. Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell. Free Radic Biol Med. 2020;160:92\u2013102.","journal-title":"Free Radic Biol Med"},{"key":"1342_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.114359","volume":"249","author":"H Tao","year":"2023","unstructured":"Tao H, Zhao H, Mo A, et al. VX-765 attenuates silica-induced lung inflammatory injury and fibrosis by modulating alveolar macrophages pyroptosis in mice. Ecotoxicol Environ Saf. 2023;249:114359.","journal-title":"Ecotoxicol Environ Saf"},{"key":"1342_CR24","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1080\/15548627.2020.1810918","volume":"17","author":"X Chen","year":"2021","unstructured":"Chen X, Li J, Kang R, Klionsky DJ, Tang D. Ferroptosis: machinery and regulation. Autophagy. 2021;17:2054\u201381.","journal-title":"Autophagy"},{"key":"1342_CR25","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.freeradbiomed.2023.06.019","volume":"206","author":"T Ye","year":"2023","unstructured":"Ye T, Yang W, Gao T, et al. Trastuzumab-induced cardiomyopathy via ferroptosis-mediated mitochondrial dysfunction. Free Radic Biol Med. 2023;206:143\u201361.","journal-title":"Free Radic Biol Med"},{"key":"1342_CR26","doi-asserted-by":"publisher","DOI":"10.1111\/1744-7917.13495","author":"W Shi","year":"2025","unstructured":"Shi W, He L, Li R, Cao J. Role of mitochondrial complex I genes in host plant expansion of Bactrocera tau (Tephritidae: Diptera) by CRISPR\/Cas9 system. Insect Sci. 2025. https:\/\/doi.org\/10.1111\/1744-7917.13495.","journal-title":"Insect Sci"},{"key":"1342_CR27","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1186\/s13287-023-03596-x","volume":"14","author":"M Jiang","year":"2023","unstructured":"Jiang M, Song Y, Chen X, et al. COX6A2 deficiency leads to cardiac remodeling in human pluripotent stem cell-derived cardiomyocytes. Stem Cell Res Ther. 2023;14:357.","journal-title":"Stem Cell Res Ther"},{"key":"1342_CR28","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/nature19359","volume":"537","author":"J Gu","year":"2016","unstructured":"Gu J, Wu M, Guo R, et al. The architecture of the mammalian respirasome. Nature. 2016;537:639\u201343.","journal-title":"Nature"},{"key":"1342_CR29","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/j.ajhg.2008.03.020","volume":"82","author":"O Barel","year":"2008","unstructured":"Barel O, Shorer Z, Flusser H, et al. Mitochondrial complex III deficiency associated with a homozygous mutation in UQCRQ. Am J Hum Genet. 2008;82:1211\u20136.","journal-title":"Am J Hum Genet"},{"key":"1342_CR30","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/humu.23210","volume":"38","author":"F Baertling","year":"2017","unstructured":"Baertling F, Al-Murshedi F, Sanchez-Caballero L, et al. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive. Hum Mutat. 2017;38:692\u2013703.","journal-title":"Hum Mutat"},{"key":"1342_CR31","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1086\/321282","volume":"69","author":"D Astuti","year":"2001","unstructured":"Astuti D, Latif F, Dallol A, et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet. 2001;69:49\u201354.","journal-title":"Am J Hum Genet"},{"key":"1342_CR32","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00109-020-02004-8","volume":"99","author":"S Javadov","year":"2021","unstructured":"Javadov S, Jang S, Chapa-Dubocq XR, Khuchua Z, Camara AK. Mitochondrial respiratory supercomplexes in mammalian cells: structural versus functional role. J Mol Med (Berl). 2021;99:57\u201373.","journal-title":"J Mol Med (Berl)"},{"key":"1342_CR33","first-page":"555","volume":"44","author":"JJ Li","year":"2022","unstructured":"Li JJ, Wu SF, Bai FX. Action mechanism of Ethambutol Tablets on Pulmonary Tuberculosis Rat Model Based on Janus Kinase\/Signal Transducer and Activator of Transcription Signaling Pathway. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2022;44:555\u201362.","journal-title":"Zhongguo Yi Xue Ke Xue Yuan Xue Bao"},{"key":"1342_CR34","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00018-023-04890-w","volume":"80","author":"RH Liou","year":"2023","unstructured":"Liou RH, Chen SW, Cheng HC, et al. The efficient induction of human retinal ganglion-like cells provides a platform for studying optic neuropathies. Cell Mol Life Sci. 2023;80:239.","journal-title":"Cell Mol Life Sci"},{"key":"1342_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030087","volume":"3","author":"R Colangeli","year":"2007","unstructured":"Colangeli R, Helb D, Vilch\u00e8ze C, et al. Transcriptional regulation of multi-drug tolerance and antibiotic-induced responses by the histone-like protein Lsr2 in M. tuberculosis. PLoS Pathog. 2007;3:e87.","journal-title":"PLoS Pathog"},{"key":"1342_CR36","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1111\/j.1742-4658.2006.05289.x","volume":"273","author":"K Sharma","year":"2006","unstructured":"Sharma K, Gupta M, Krupa A, Srinivasan N, Singh Y. EmbR, a regulatory protein with ATPase activity, is a substrate of multiple serine\/threonine kinases and phosphatase in Mycobacterium tuberculosis. FEBS J. 2006;273:2711\u201321.","journal-title":"FEBS J"},{"key":"1342_CR37","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.taap.2008.11.006","volume":"235","author":"H Chung","year":"2009","unstructured":"Chung H, Yoon YH, Hwang JJ, Cho KS, Koh JY, Kim JG. Ethambutol-induced toxicity is mediated by zinc and lysosomal membrane permeabilization in cultured retinal cells. Toxicol Appl Pharmacol. 2009;235:163\u201370.","journal-title":"Toxicol Appl Pharmacol"},{"key":"1342_CR38","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.mito.2009.11.004","volume":"10","author":"V Guillet","year":"2010","unstructured":"Guillet V, Chevrollier A, Cassereau J, et al. Ethambutol-induced optic neuropathy linked to OPA1 mutation and mitochondrial toxicity. Mitochondrion. 2010;10:115\u201324.","journal-title":"Mitochondrion"},{"key":"1342_CR39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202105043","author":"B Gan","year":"2021","unstructured":"Gan B. Mitochondrial regulation of ferroptosis. J Cell Biol. 2021. https:\/\/doi.org\/10.1083\/jcb.202105043.","journal-title":"J Cell Biol"},{"key":"1342_CR40","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41580-024-00703-5","volume":"25","author":"SJ Dixon","year":"2024","unstructured":"Dixon SJ, Olzmann JA. The cell biology of ferroptosis. Nat Rev Mol Cell Biol. 2024;25:424\u201342.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1342_CR41","doi-asserted-by":"publisher","first-page":"3480","DOI":"10.1158\/0008-5472.CAN-20-2936","volume":"81","author":"J Goncalves","year":"2021","unstructured":"Goncalves J, Moog S, Morin A, et al. Loss of SDHB promotes dysregulated iron homeostasis, oxidative stress, and sensitivity to ascorbate. Cancer Res. 2021;81:3480\u201394.","journal-title":"Cancer Res"},{"key":"1342_CR42","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.mito.2014.06.001","volume":"19 Pt A","author":"MS Hwang","year":"2014","unstructured":"Hwang MS, Rohlena J, Dong LF, Neuzil J, Grimm S. Powerhouse down: complex II dissociation in the respiratory chain. Mitochondrion. 2014;19 Pt A:20\u20138.","journal-title":"Mitochondrion"},{"key":"1342_CR43","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948781","volume":"21","author":"J Li","year":"2020","unstructured":"Li J, Sun YBY, Chen W, et al. Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS. EMBO Rep. 2020;21:e48781.","journal-title":"EMBO Rep"},{"key":"1342_CR44","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.tranon.2016.09.009","volume":"9","author":"H Wang","year":"2016","unstructured":"Wang H, Chen Y, Wu G. SDHB deficiency promotes TGFbeta-mediated invasion and metastasis of colorectal cancer through transcriptional repression complex SNAIL1-SMAD3\/4. Transl Oncol. 2016;9:512\u201320.","journal-title":"Transl Oncol"},{"key":"1342_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13040986","author":"N Zhao","year":"2025","unstructured":"Zhao N, Li S, Wu H, et al. Ferroptosis: an energetic villain of age-related macular degeneration. Biomedicines. 2025. https:\/\/doi.org\/10.3390\/biomedicines13040986.","journal-title":"Biomedicines"},{"key":"1342_CR46","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13101367","author":"HY Tian","year":"2023","unstructured":"Tian HY, Huang BY, Nie HF, et al. The interplay between mitochondrial dysfunction and ferroptosis during ischemia-associated central nervous system diseases. Brain Sci. 2023. https:\/\/doi.org\/10.3390\/brainsci13101367.","journal-title":"Brain Sci"},{"key":"1342_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252313042","author":"M Zhou","year":"2024","unstructured":"Zhou M, Xu K, Ge J, et al. Targeting ferroptosis in Parkinson\u2019s disease: mechanisms and emerging therapeutic strategies. Int J Mol Sci. 2024. https:\/\/doi.org\/10.3390\/ijms252313042.","journal-title":"Int J Mol Sci"},{"key":"1342_CR48","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nature15514","volume":"526","author":"J Shi","year":"2015","unstructured":"Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660\u20135.","journal-title":"Nature"},{"key":"1342_CR49","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nature11729","volume":"493","author":"MT Heneka","year":"2013","unstructured":"Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice. Nature. 2013;493:674\u20138.","journal-title":"Nature"},{"key":"1342_CR50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242316811","author":"W Lv","year":"2023","unstructured":"Lv W, Wu X, Dou Y, et al. Homer1 protects against retinal ganglion cell pyroptosis by inhibiting endoplasmic reticulum stress-associated TXNIP\/NLRP3 inflammasome activation after middle cerebral artery occlusion-induced retinal ischemia. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms242316811.","journal-title":"Int J Mol Sci"},{"key":"1342_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00372-w","volume":"15","author":"H Chen","year":"2020","unstructured":"Chen H, Deng Y, Gan X, et al. NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma. Mol Neurodegener. 2020;15:26.","journal-title":"Mol Neurodegener"},{"key":"1342_CR52","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/s41420-024-01874-y","volume":"10","author":"M Park","year":"2024","unstructured":"Park M, Park S, Choi Y, et al. The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages. Cell Death Discov. 2024;10:144.","journal-title":"Cell Death Discov"},{"key":"1342_CR53","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1080\/15569527.2018.1539010","volume":"38","author":"Y Karakurt","year":"2019","unstructured":"Karakurt Y, Suleyman H, Keskin Cimen F, et al. The effects of lutein on optic nerve injury induced by ethambutol and isoniazid: an experimental study. Cutan Ocul Toxicol. 2019;38:136\u201340.","journal-title":"Cutan Ocul Toxicol"},{"key":"1342_CR54","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3109\/15569527.2012.759958","volume":"32","author":"A Sahin","year":"2013","unstructured":"Sahin A, Kursat Cingu A, Kaya S, et al. The protective effects of caffeic acid phenethyl ester in isoniazid and ethambutol-induced ocular toxicity of rats. Cutan Ocul Toxicol. 2013;32:228\u201333.","journal-title":"Cutan Ocul Toxicol"}],"container-title":["Human Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-025-01342-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13577-025-01342-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-025-01342-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:02:11Z","timestamp":1768978931000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13577-025-01342-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["1342"],"URL":"https:\/\/doi.org\/10.1007\/s13577-025-01342-4","relation":{},"ISSN":["1749-0774"],"issn-type":[{"value":"1749-0774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"8 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The animal experiments were conducted by the \u201cGuiding Principles in the Care and Use of Animals\u201d (China) and approved by Shengyuan Life Sciences and Technology (Anji) Co., Ltd (approval number: 2025003).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"37"}}