{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T14:39:14Z","timestamp":1772289554582,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1458,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Herein we study the effects of the mitochondrial complex II inhibitor malonate on its primary target, the mitochondrion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Malonate induces mitochondrial potential collapse, mitochondrial swelling, cytochrome <jats:italic>c<\/jats:italic> (Cyt <jats:italic>c<\/jats:italic>) release and depletes glutathione (GSH) and nicotinamide adenine dinucleotide coenzyme (NAD(P)H) stores in brain\u2010isolated mitochondria.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Although, mitochondrial potential collapse was almost immediate after malonate addition, mitochondrial swelling was not evident before 15\u2003min of drug presence. This latter effect was blocked by cyclosporin A (CSA), Ruthenium Red (RR), magnesium, catalase, GSH and vitamin E.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Malonate added to SH\u2010SY5Y cell cultures produced a marked loss of cell viability together with the release of Cyt <jats:italic>c<\/jats:italic> and depletion of GSH and NAD(P)H concentrations. All these effects were not apparent in SH\u2010SY5Y cells overexpressing Bcl\u2010xL.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When GSH concentrations were lowered with buthionine sulphoximine, cytoprotection afforded by Bcl\u2010xL overexpression was not evident anymore.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Taken together, all these data suggest that malonate causes a rapid mitochondrial potential collapse and reactive oxygen species production that overwhelms mitochondrial antioxidant capacity and leads to mitochondrial swelling. Further permeability transition pore opening and the subsequent release of proapoptotic factors such as Cyt <jats:italic>c<\/jats:italic> could therefore be, at least in part, responsible for malonate\u2010induced toxicity.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>144<\/jats:bold>, 528\u2013537. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706069\">10.1038\/sj.bjp.0706069<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706069","type":"journal-article","created":{"date-parts":[[2005,1,17]],"date-time":"2005-01-17T18:25:43Z","timestamp":1105986343000},"page":"528-537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Malonate induces cell death <i>via<\/i> mitochondrial potential collapse and delayed swelling through an ROS\u2010dependent pathway"],"prefix":"10.1111","volume":"144","author":[{"given":"Francisco J","family":"Fernandez\u2010Gomez","sequence":"first","affiliation":[]},{"given":"Maria F","family":"Galindo","sequence":"additional","affiliation":[]},{"given":"Maria","family":"G\u00f3mez\u2010L\u00e1zaro","sequence":"additional","affiliation":[]},{"given":"Victor J","family":"Yuste","sequence":"additional","affiliation":[]},{"given":"Joan X","family":"Comella","sequence":"additional","affiliation":[]},{"given":"Norberto","family":"Aguirre","sequence":"additional","affiliation":[]},{"given":"Joaqu\u00edn","family":"Jord\u00e1n","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69031196.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002361200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb03633.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1127"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.5520080315"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0021-9258(18)54033-3","article-title":"Modulation of the mitochondrial cyclosporin A\u2010sensitive permeability transition pore. 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