{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:50:09Z","timestamp":1790189409011,"version":"4.1.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003382","name":"MEXT | JST | Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","award":["20348438"],"award-info":[{"award-number":["20348438"]}],"id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003382","name":"MEXT | JST | Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","award":["20348438"],"award-info":[{"award-number":["20348438"]}],"id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003382","name":"MEXT | JST | Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","award":["20348438"],"award-info":[{"award-number":["20348438"]}],"id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H02772"],"award-info":[{"award-number":["22H02772"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K19395"],"award-info":[{"award-number":["22K19395"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02869"],"award-info":[{"award-number":["24K02869"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K28237"],"award-info":[{"award-number":["23K28237"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H05277"],"award-info":[{"award-number":["18H05277"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K19397"],"award-info":[{"award-number":["22K19397"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["21H05269"],"award-info":[{"award-number":["21H05269"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["21H05263"],"award-info":[{"award-number":["21H05263"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["21H05258"],"award-info":[{"award-number":["21H05258"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["23K20040"],"award-info":[{"award-number":["23K20040"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008608","name":"Sumitomo Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009024","name":"MEXT | JST | Exploratory Research for Advanced Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP15km0908001"],"award-info":[{"award-number":["JP15km0908001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP15km0908001"],"award-info":[{"award-number":["JP15km0908001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The presence of redox-active molecules containing catenated sulfur atoms (supersulfides) in living organisms has led to a review of the concepts of redox biology and its translational strategy. Glutathione (GSH) is the body\u2019s primary detoxifier and antioxidant, and its oxidized form (GSSG) has been considered as a marker of oxidative status. However, we report that GSSG, but not reduced GSH, prevents ischemic supersulfide catabolism-associated heart failure in male mice by electrophilic modification of dynamin-related protein (Drp1). In healthy exercised hearts, the redox-sensitive Cys644 of Drp1 is highly S-glutathionylated. Nearly 40% of Cys644 is normally polysulfidated, which is a preferential target for GSSG-mediated S-glutathionylation. Cys644 S-glutathionylation is resistant to Drp1 depolysulfidation-dependent mitochondrial hyperfission and myocardial dysfunction caused by hypoxic stress. MD simulation of Drp1 structure and site-directed mutagenetic analysis reveal a functional interaction between Cys644 and a critical phosphorylation site Ser637, through Glu640. Bulky modification at Cys644 via polysulfidation or S-glutathionylation reduces Drp1 activity by disrupting Ser637-Glu640-Cys644 interaction. Disruption of Cys644 S-glutathionylation nullifies the cardioprotective effect of GSSG against heart failure after myocardial infarction. Our findings suggest a therapeutic potential of supersulfide-based Cys bulking on Drp1 for ischemic heart disease.<\/jats:p>","DOI":"10.1038\/s41467-024-55661-5","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T02:25:47Z","timestamp":1735871147000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Polysulfur-based bulking of dynamin-related protein 1 prevents ischemic sulfide catabolism and heart failure in mice"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-3994","authenticated-orcid":false,"given":"Akiyuki","family":"Nishimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-7823","authenticated-orcid":false,"given":"Seiryo","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9766-4636","authenticated-orcid":false,"given":"Xiaokang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kowit","family":"Hengphasatporn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2380-4453","authenticated-orcid":false,"given":"Keitaro","family":"Umezawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8806-1745","authenticated-orcid":false,"given":"Makoto","family":"Sanbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1059-5883","authenticated-orcid":false,"given":"Masumi","family":"Hirabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-911X","authenticated-orcid":false,"given":"Yuri","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6702-526X","authenticated-orcid":false,"given":"Yuko","family":"Ibuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Kumagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7389-3693","authenticated-orcid":false,"given":"Kenta","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2527-3526","authenticated-orcid":false,"given":"Yasunari","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-6327","authenticated-orcid":false,"given":"Yasuteru","family":"Urano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-6007","authenticated-orcid":false,"given":"Yasuteru","family":"Shigeta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0623-1710","authenticated-orcid":false,"given":"Takaaki","family":"Akaike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2587-5458","authenticated-orcid":false,"given":"Motohiro","family":"Nishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"55661_CR1","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nrcardio.2016.203","volume":"14","author":"DA Brown","year":"2017","unstructured":"Brown, D. A. et al. Expert consensus document: mitochondrial function as a therapeutic target in heart failure. Nat. Rev. Cardiol. 14, 238\u2013250 (2017).","journal-title":"Nat. Rev. Cardiol."},{"key":"55661_CR2","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1161\/CIRCULATIONAHA.118.036259","volume":"139","author":"AA Kumar","year":"2019","unstructured":"Kumar, A. A., Kelly, D. P. & Chirinos, J. A. Mitochondrial dysfunction in heart failure with preserved ejection fraction. Circulation 139, 1435\u20131450 (2019).","journal-title":"Circulation"},{"key":"55661_CR3","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0116","volume":"350","author":"T Wai","year":"2015","unstructured":"Wai, T. et al. Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science 350, aad0116 (2015).","journal-title":"Science"},{"key":"55661_CR4","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.cmet.2017.09.023","volume":"26","author":"M Song","year":"2017","unstructured":"Song, M., Franco, A., Fleischer, J. A., Zhang, L. & Dorn, G. W. 2nd Abrogating mitochondrial dynamics in mouse hearts accelerates mitochondrial senescence. Cell Metab. 26, 872\u2013883.e875 (2017).","journal-title":"Cell Metab."},{"key":"55661_CR5","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cmet.2014.12.011","volume":"21","author":"M Song","year":"2015","unstructured":"Song, M., Mihara, K., Chen, Y., Scorrano, L. & Dorn, G. W. 2nd Mitochondrial fission and fusion factors reciprocally orchestrate mitophagic culling in mouse hearts and cultured fibroblasts. Cell Metab. 21, 273\u2013286 (2015).","journal-title":"Cell Metab."},{"key":"55661_CR6","doi-asserted-by":"publisher","first-page":"eaat5185","DOI":"10.1126\/scisignal.aat5185","volume":"11","author":"A Nishimura","year":"2018","unstructured":"Nishimura, A. et al. Hypoxia-induced interaction of filamin with Drp1 causes mitochondrial hyperfission-associated myocardial senescence. Sci. Signal 11, eaat5185 (2018).","journal-title":"Sci. Signal"},{"key":"55661_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.127","volume":"3","author":"J Zuo","year":"2022","unstructured":"Zuo, J. et al. Redox signaling at the crossroads of human health and disease. MedComm (2020) 3, e127 (2022).","journal-title":"MedComm (2020)"},{"key":"55661_CR8","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/ejhf.1320","volume":"21","author":"A van der Pol","year":"2019","unstructured":"van der Pol, A., van Gilst, W. H., Voors, A. A. & van der Meer, P. Treating oxidative stress in heart failure: past, present and future. Eur. J. Heart Fail 21, 425\u2013435 (2019).","journal-title":"Eur. J. Heart Fail"},{"key":"55661_CR9","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3389\/fcvm.2015.00029","volume":"2","author":"K Goszcz","year":"2015","unstructured":"Goszcz, K. et al. Antioxidants in cardiovascular therapy: panacea or false hope? Front Cardiovasc Med. 2, 29 (2015).","journal-title":"Front Cardiovasc Med"},{"key":"55661_CR10","doi-asserted-by":"publisher","first-page":"3784","DOI":"10.3390\/jcm11133784","volume":"11","author":"G Pavlidis","year":"2022","unstructured":"Pavlidis, G. Oxidative stress and antioxidant therapy in cardiovascular diseases-clinical challenge. J. Clin. Med. 11, 3784 (2022).","journal-title":"J. Clin. Med"},{"key":"55661_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3164\/jcbn.21-84","volume":"70","author":"A Nishimura","year":"2022","unstructured":"Nishimura, A., Tanaka, T., Kato, Y., Nishiyama, K. & Nishida, M. Cardiac robustness regulated by reactive sulfur species. J. Clin. Biochem Nutr. 70, 1\u20136 (2022).","journal-title":"J. Clin. Biochem Nutr."},{"key":"55661_CR12","doi-asserted-by":"publisher","first-page":"7606","DOI":"10.1073\/pnas.1321232111","volume":"111","author":"T Ida","year":"2014","unstructured":"Ida, T. et al. Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. Proc. Natl Acad. Sci. USA 111, 7606\u20137611 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"55661_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01311-y","volume":"8","author":"T Akaike","year":"2017","unstructured":"Akaike, T. et al. Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. Nat. Commun. 8, 1177 (2017).","journal-title":"Nat. Commun."},{"key":"55661_CR14","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.3390\/molecules21121721","volume":"21","author":"S Kasamatsu","year":"2016","unstructured":"Kasamatsu, S. et al. Redox signaling regulated by cysteine persulfide and protein polysulfidation. Molecules 21, 1721 (2016).","journal-title":"Molecules"},{"key":"55661_CR15","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3390\/md21010052","volume":"21","author":"X Tang","year":"2023","unstructured":"Tang, X. et al. Echinochrome prevents sulfide catabolism-associated chronic heart failure after myocardial infarction in mice. Mar. Drugs 21, 52 (2023).","journal-title":"Mar. Drugs"},{"key":"55661_CR16","doi-asserted-by":"publisher","first-page":"ra72","DOI":"10.1126\/scisignal.2000464","volume":"2","author":"AK Mustafa","year":"2009","unstructured":"Mustafa, A. K. et al. H2S signals through protein S-sulfhydration. Sci. Signal 2, ra72 (2009).","journal-title":"Sci. Signal"},{"key":"55661_CR17","doi-asserted-by":"publisher","first-page":"ra87","DOI":"10.1126\/scisignal.2005478","volume":"7","author":"Z Altaany","year":"2014","unstructured":"Altaany, Z., Ju, Y., Yang, G. & Wang, R. The coordination of S-sulfhydration, S-nitrosylation, and phosphorylation of endothelial nitric oxide synthase by hydrogen sulfide. Sci. Signal 7, ra87 (2014).","journal-title":"Sci. Signal"},{"key":"55661_CR18","doi-asserted-by":"publisher","first-page":"eaaw1920","DOI":"10.1126\/scisignal.aaw1920","volume":"12","author":"A Nishimura","year":"2019","unstructured":"Nishimura, A. et al. Depolysulfidation of Drp1 induced by low-dose methylmercury exposure increases cardiac vulnerability to hemodynamic overload. Sci. Signal 12, eaaw1920 (2019).","journal-title":"Sci. Signal"},{"key":"55661_CR19","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.freeradbiomed.2009.12.022","volume":"48","author":"ML Circu","year":"2010","unstructured":"Circu, M. L. & Aw, T. Y. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 48, 749\u2013762 (2010).","journal-title":"Free Radic. Biol. Med"},{"key":"55661_CR20","doi-asserted-by":"publisher","first-page":"196","DOI":"10.3389\/fphar.2014.00196","volume":"5","author":"K Aquilano","year":"2014","unstructured":"Aquilano, K., Baldelli, S. & Ciriolo, M. R. Glutathione: new roles in redox signaling for an old antioxidant. Front Pharm. 5, 196 (2014).","journal-title":"Front Pharm."},{"key":"55661_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101693","volume":"37","author":"NA Rashdan","year":"2020","unstructured":"Rashdan, N. A., Shrestha, B. & Pattillo, C. B. S-glutathionylation, friend or foe in cardiovascular health and disease. Redox Biol. 37, 101693 (2020).","journal-title":"Redox Biol."},{"key":"55661_CR22","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1021\/acs.jproteome.8b00986","volume":"18","author":"GC VanHecke","year":"2019","unstructured":"VanHecke, G. C., Abeywardana, M. Y. & Ahn, Y. H. Proteomic identification of protein glutathionylation in cardiomyocytes. J. Proteome Res. 18, 1806\u20131818 (2019).","journal-title":"J. Proteome Res"},{"key":"55661_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27428-9","volume":"12","author":"Y Guo","year":"2021","unstructured":"Guo, Y. et al. Oxidative stress-induced FABP5 S-glutathionylation protects against acute lung injury by suppressing inflammation in macrophages. Nat. Commun. 12, 7094 (2021).","journal-title":"Nat. Commun."},{"key":"55661_CR24","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.molmet.2018.11.012","volume":"21","author":"TM Moore","year":"2019","unstructured":"Moore, T. M. et al. The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle. Mol. Metab. 21, 51\u201367 (2019).","journal-title":"Mol. Metab."},{"key":"55661_CR25","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s00424-019-02258-3","volume":"472","author":"T Tanaka","year":"2020","unstructured":"Tanaka, T. et al. Mitochondrial dynamics in exercise physiology. Pflug. Arch. 472, 137\u2013153 (2020).","journal-title":"Pflug. Arch."},{"key":"55661_CR26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.jphs.2023.12.008","volume":"154","author":"A Nishimura","year":"2024","unstructured":"Nishimura, A. et al. Supersulfide prevents cigarette smoke extract-induced mitochondria hyperfission and cardiomyocyte early senescence by inhibiting Drp1-filamin complex formation. J. Pharm. Sci. 154, 127\u2013135 (2024).","journal-title":"J. Pharm. Sci."},{"key":"55661_CR27","doi-asserted-by":"publisher","first-page":"3565","DOI":"10.1016\/j.celrep.2018.05.054","volume":"23","author":"YM Kim","year":"2018","unstructured":"Kim, Y. M. et al. Redox regulation of mitochondrial fission protein Drp1 by protein disulfide isomerase limits endothelial senescence. Cell Rep. 23, 3565\u20133578 (2018).","journal-title":"Cell Rep."},{"key":"55661_CR28","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1126\/science.1171091","volume":"324","author":"DH Cho","year":"2009","unstructured":"Cho, D. H. et al. S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324, 102\u2013105 (2009).","journal-title":"Science"},{"key":"55661_CR29","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.bbrc.2010.03.093","volume":"395","author":"N Mishra","year":"2010","unstructured":"Mishra, N. et al. Inhibition of mitochondrial division through covalent modification of Drp1 protein by 15 deoxy-Delta(12,14)-prostaglandin J2. Biochem Biophys. Res. Commun. 395, 17\u201324 (2010).","journal-title":"Biochem Biophys. Res. Commun."},{"key":"55661_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102519","volume":"58","author":"D Wu","year":"2022","unstructured":"Wu, D., Tan, B., Sun, Y. & Hu, Q. Cystathionine gamma lyase S-sulfhydrates Drp1 to ameliorate heart dysfunction. Redox Biol. 58, 102519 (2022).","journal-title":"Redox Biol."},{"key":"55661_CR31","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1152\/jappl.1996.81.5.2199","volume":"81","author":"J Vina","year":"1996","unstructured":"Vina, J. et al. Exercise causes blood glutathione oxidation in chronic obstructive pulmonary disease: prevention by O2 therapy. J. Appl Physiol. (1985) 81, 2198\u20132202 (1996).","journal-title":"J. Appl Physiol. (1985)"},{"key":"55661_CR32","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1007\/s00415-010-5584-6","volume":"257","author":"A Elokda","year":"2010","unstructured":"Elokda, A., DiFrancisco-Donoghue, J., Lamberg, E. M. & Werner, W. G. Effects of exercise induced oxidative stress on glutathione levels in Parkinson\u2019s disease on and off medication. J. Neurol. 257, 1648\u20131653 (2010).","journal-title":"J. Neurol."},{"key":"55661_CR33","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.ijcard.2017.12.004","volume":"258","author":"N Chakouri","year":"2018","unstructured":"Chakouri, N. et al. Stress-induced protein S-glutathionylation and phosphorylation crosstalk in cardiac sarcomeric proteins - Impact on heart function. Int J. Cardiol. 258, 207\u2013216 (2018).","journal-title":"Int J. Cardiol."},{"key":"55661_CR34","doi-asserted-by":"publisher","first-page":"9346","DOI":"10.1002\/anie.201804309","volume":"57","author":"K Umezawa","year":"2018","unstructured":"Umezawa, K., Kamiya, M. & Urano, Y. A reversible fluorescent probe for real-time live-cell imaging and quantification of endogenous hydropolysulfides. Angew. Chem. Int Ed. Engl. 57, 9346\u20139350 (2018).","journal-title":"Angew. Chem. Int Ed. Engl."},{"key":"55661_CR35","doi-asserted-by":"publisher","first-page":"7131","DOI":"10.1073\/pnas.1302193110","volume":"110","author":"VS Lin","year":"2013","unstructured":"Lin, V. S., Lippert, A. R. & Chang, C. J. Cell-trappable fluorescent probes for endogenous hydrogen sulfide signaling and imaging H2O2-dependent H2S production. Proc. Natl Acad. Sci. USA 110, 7131\u20137135 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"55661_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23363-x","volume":"12","author":"E Marutani","year":"2021","unstructured":"Marutani, E. et al. Sulfide catabolism ameliorates hypoxic brain injury. Nat. Commun. 12, 3108 (2021).","journal-title":"Nat. Commun."},{"key":"55661_CR37","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1039\/C6CC08372B","volume":"53","author":"Y Takano","year":"2017","unstructured":"Takano, Y. et al. Development of a reversible fluorescent probe for reactive sulfur species, sulfane sulfur, and its biological application. Chem. Commun. (Camb.) 53, 1064\u20131067 (2017).","journal-title":"Chem. Commun. (Camb.)"},{"key":"55661_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/srep34424","volume":"6","author":"H Daijo","year":"2016","unstructured":"Daijo, H. et al. Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner. Sci. Rep. 6, 34424 (2016).","journal-title":"Sci. Rep."},{"key":"55661_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11008-3","volume":"7","author":"CA Francy","year":"2017","unstructured":"Francy, C. A., Clinton, R. W., Frohlich, C., Murphy, C. & Mears, J. A. Cryo-EM studies of Drp1 reveal cardiolipin interactions that activate the helical oligomer. Sci. Rep. 7, 10744 (2017).","journal-title":"Sci. Rep."},{"key":"55661_CR40","doi-asserted-by":"publisher","first-page":"4466","DOI":"10.1091\/mbc.E15-08-0591","volume":"26","author":"R Liu","year":"2015","unstructured":"Liu, R. & Chan, D. C. The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1. Mol. Biol. Cell 26, 4466\u20134477 (2015).","journal-title":"Mol. Biol. Cell"},{"key":"55661_CR41","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1074\/jbc.M115.680025","volume":"291","author":"RW Clinton","year":"2016","unstructured":"Clinton, R. W., Francy, C. A., Ramachandran, R., Qi, X. & Mears, J. A. Dynamin-related protein 1 oligomerization in solution impairs functional interactions with membrane-anchored mitochondrial fission factor. J. Biol. Chem. 291, 478\u2013492 (2016).","journal-title":"J. Biol. Chem."},{"key":"55661_CR42","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41586-018-0211-2","volume":"558","author":"R Kalia","year":"2018","unstructured":"Kalia, R. et al. Structural basis of mitochondrial receptor binding and constriction by DRP1. Nature 558, 401\u2013405 (2018).","journal-title":"Nature"},{"key":"55661_CR43","doi-asserted-by":"publisher","first-page":"21583","DOI":"10.1074\/jbc.C700083200","volume":"282","author":"CR Chang","year":"2007","unstructured":"Chang, C. R. & Blackstone, C. Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J. Biol. Chem. 282, 21583\u201321587 (2007).","journal-title":"J. Biol. Chem."},{"key":"55661_CR44","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/sj.embor.7401062","volume":"8","author":"JT Cribbs","year":"2007","unstructured":"Cribbs, J. T. & Strack, S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 8, 939\u2013944 (2007).","journal-title":"EMBO Rep."},{"key":"55661_CR45","doi-asserted-by":"publisher","first-page":"15803","DOI":"10.1073\/pnas.0808249105","volume":"105","author":"GM Cereghetti","year":"2008","unstructured":"Cereghetti, G. M. et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl Acad. Sci. USA 105, 15803\u201315808 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"55661_CR46","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.freeradbiomed.2014.11.013","volume":"80","author":"LB Poole","year":"2015","unstructured":"Poole, L. B. The basics of thiols and cysteines in redox biology and chemistry. Free Radic. Biol. Med. 80, 148\u2013157 (2015).","journal-title":"Free Radic. Biol. Med"},{"key":"55661_CR47","doi-asserted-by":"publisher","first-page":"26866","DOI":"10.1074\/jbc.M115.672816","volume":"290","author":"E Cuevasanta","year":"2015","unstructured":"Cuevasanta, E. et al. Reaction of hydrogen sulfide with disulfide and sulfenic acid to form the strongly nucleophilic persulfide. J. Biol. Chem. 290, 26866\u201326880 (2015).","journal-title":"J. Biol. Chem."},{"key":"55661_CR48","doi-asserted-by":"publisher","first-page":"L1590","DOI":"10.1152\/ajplung.00365.2006","volume":"292","author":"C Kariya","year":"2007","unstructured":"Kariya, C. et al. A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration. Am. J. Physiol. Lung Cell Mol. Physiol. 292, L1590\u2013L1597 (2007).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"55661_CR49","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1023\/A:1012381928535","volume":"66","author":"AN Tsyupko","year":"2001","unstructured":"Tsyupko, A. N., Dudnik, L. B., Evstigneeva, R. P. & Alessenko, A. V. Effects of reduced and oxidized glutathione on sphingomyelinase activity and contents of sphingomyelin and lipid peroxidation products in murine liver. Biochem. (Mosc.) 66, 1028\u20131034 (2001).","journal-title":"Biochem. (Mosc.)"},{"key":"55661_CR50","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.freeradbiomed.2016.12.006","volume":"109","author":"DE Handy","year":"2017","unstructured":"Handy, D. E. & Loscalzo, J. Responses to reductive stress in the cardiovascular system. Free Radic. Biol. Med. 109, 114\u2013124 (2017).","journal-title":"Free Radic. Biol. Med"},{"key":"55661_CR51","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41589-023-01461-9","volume":"20","author":"AC Murphy","year":"2024","unstructured":"Murphy, A. C. & McReynolds, M. R. Toying with reductive stress. Nat. Chem. Biol. 20, 542\u2013543 (2024).","journal-title":"Nat. Chem. Biol."},{"key":"55661_CR52","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1089\/ars.2019.7803","volume":"32","author":"W Xiao","year":"2020","unstructured":"Xiao, W. & Loscalzo, J. Metabolic responses to reductive stress. Antioxid. Redox Signal 32, 1330\u20131347 (2020).","journal-title":"Antioxid. Redox Signal"},{"key":"55661_CR53","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/s41589-023-01460-w","volume":"20","author":"X Pan","year":"2024","unstructured":"Pan, X. et al. A genetically encoded tool to increase cellular NADH\/NAD(+) ratio in living cells. Nat. Chem. Biol. 20, 594\u2013604 (2024).","journal-title":"Nat. Chem. Biol."},{"key":"55661_CR54","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1089\/ars.2012.4914","volume":"18","author":"AC Brewer","year":"2013","unstructured":"Brewer, A. C., Mustafi, S. B., Murray, T. V., Rajasekaran, N. S. & Benjamin, I. J. Reductive stress linked to small HSPs, G6PD, and Nrf2 pathways in heart disease. Antioxid. Redox Signal 18, 1114\u20131127 (2013).","journal-title":"Antioxid. Redox Signal"},{"key":"55661_CR55","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1161\/HYPERTENSIONAHA.109.147066","volume":"55","author":"X Zhang","year":"2010","unstructured":"Zhang, X. et al. Involvement of reductive stress in the cardiomyopathy in transgenic mice with cardiac-specific overexpression of heat shock protein 27. Hypertension 55, 1412\u20131417 (2010).","journal-title":"Hypertension"},{"key":"55661_CR56","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1089\/ars.2019.7808","volume":"32","author":"G Shanmugam","year":"2020","unstructured":"Shanmugam, G. et al. Reductive stress causes pathological cardiac remodeling and diastolic dysfunction. Antioxid. Redox Signal 32, 1293\u20131312 (2020).","journal-title":"Antioxid. Redox Signal"},{"key":"55661_CR57","doi-asserted-by":"publisher","first-page":"11641","DOI":"10.1074\/jbc.M117.788547","volume":"292","author":"AP Landry","year":"2017","unstructured":"Landry, A. P., Ballou, D. P. & Banerjee, R. H(2)S oxidation by nanodisc-embedded human sulfide quinone oxidoreductase. J. Biol. Chem. 292, 11641\u201311649 (2017).","journal-title":"J. Biol. Chem."},{"key":"55661_CR58","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1080\/10715760000300051","volume":"32","author":"KS Seiler","year":"2000","unstructured":"Seiler, K. S. & Starnes, J. W. Exogenous GSH protection during hypoxia-reoxygenation of the isolated rat heart: impact of hypoxia duration. Free Radic. Res. 32, 41\u201355 (2000).","journal-title":"Free Radic. Res"},{"key":"55661_CR59","doi-asserted-by":"publisher","first-page":"H679","DOI":"10.1152\/ajpheart.2001.281.2.H679","volume":"281","author":"PR Ramires","year":"2001","unstructured":"Ramires, P. R. & Ji, L. L. Glutathione supplementation and training increases myocardial resistance to ischemia-reperfusion in vivo. Am. J. Physiol. Heart Circ. Physiol. 281, H679\u2013H688 (2001).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"55661_CR60","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41401-021-00650-3","volume":"43","author":"H Wang","year":"2022","unstructured":"Wang, H. et al. Exogenous glutathione exerts a therapeutic effect in ischemic stroke rats by interacting with intrastriatal dopamine. Acta Pharm. Sin. 43, 541\u2013551 (2022).","journal-title":"Acta Pharm. Sin."},{"key":"55661_CR61","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/0307-4412(83)90048-1","volume":"11","author":"R Stevens","year":"1983","unstructured":"Stevens, R., Stevens, L. & Price, N. C. The stabilities of various thiol compounds used in protein purifications. Biochem Educ. 11, 70\u201370 (1983).","journal-title":"Biochem Educ."},{"key":"55661_CR62","doi-asserted-by":"publisher","first-page":"e93358","DOI":"10.1172\/jci.insight.93358","volume":"2","author":"T Shimauchi","year":"2017","unstructured":"Shimauchi, T. et al. TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy. JCI Insight 2, e93358 (2017).","journal-title":"JCI Insight"},{"key":"55661_CR63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/9780470942390.mo150182","volume":"6","author":"P Jha","year":"2016","unstructured":"Jha, P., Wang, X. & Auwerx, J. Analysis of mitochondrial respiratory chain supercomplexes using blue native polyacrylamide gel electrophoresis (BN-PAGE). Curr. Protoc. Mouse Biol. 6, 1\u201314 (2016).","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"55661_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102514","volume":"57","author":"M Akiyama","year":"2022","unstructured":"Akiyama, M. et al. Cystine-dependent antiporters buffer against excess intracellular reactive sulfur species-induced stress. Redox Biol. 57, 102514 (2022).","journal-title":"Redox Biol."},{"key":"55661_CR65","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jphs.2024.04.005","volume":"155","author":"A Nishimura","year":"2024","unstructured":"Nishimura, A. et al. Sulfur metabolism as a new therapeutic target of heart failure. J. Pharm. Sci. 155, 75\u201383 (2024).","journal-title":"J. Pharm. Sci."},{"key":"55661_CR66","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500968","volume":"2","author":"E Doka","year":"2016","unstructured":"Doka, E. et al. A novel persulfide detection method reveals protein persulfide- and polysulfide-reducing functions of thioredoxin and glutathione systems. Sci. Adv. 2, e1500968 (2016).","journal-title":"Sci. Adv."},{"key":"55661_CR67","doi-asserted-by":"publisher","first-page":"20845","DOI":"10.3390\/ijms141020845","volume":"14","author":"A Pastore","year":"2013","unstructured":"Pastore, A. & Piemonte, F. Protein glutathionylation in cardiovascular diseases. Int J. Mol. Sci. 14, 20845\u201320876 (2013).","journal-title":"Int J. Mol. Sci."},{"key":"55661_CR68","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1089\/ars.2020.8073","volume":"34","author":"S Kasamatsu","year":"2021","unstructured":"Kasamatsu, S. et al. High-precision sulfur metabolomics innovated by a new specific probe for trapping reactive sulfur species. Antioxid. Redox Signal 34, 1407\u20131419 (2021).","journal-title":"Antioxid. Redox Signal"},{"key":"55661_CR69","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019104073","volume":"39","author":"R Acin-Perez","year":"2020","unstructured":"Acin-Perez, R. et al. A novel approach to measure mitochondrial respiration in frozen biological samples. EMBO J. 39, e104073 (2020).","journal-title":"EMBO J."},{"key":"55661_CR70","doi-asserted-by":"publisher","first-page":"e5","DOI":"10.1161\/CIRCRESAHA.117.312067","volume":"122","author":"L Sala","year":"2018","unstructured":"Sala, L. et al. MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo. Circ. Res. 122, e5\u2013e16 (2018).","journal-title":"Circ. Res"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-55661-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-55661-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-55661-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T19:02:56Z","timestamp":1735930976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-55661-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,2]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["55661"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-55661-5","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,2]]},"assertion":[{"value":"9 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2025","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":"276"}}