{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:26:42Z","timestamp":1789896402300,"version":"4.0.1"},"reference-count":43,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>ADF\/cofilin family proteins are essential regulators of actin cytoskeletal dynamics. Recent evidence also implicates cofilin in the regulation of mitochondrial function. Here, we identify new functional surfaces of cofilin that are linked with mitochondrial function and stress responses in the budding yeast S. cerevisiae. Our data links surfaces of cofilin that are involved in separable activities of actin filament disassembly or stabilisation, to the regulation of mitochondrial morphology and the activation status of Ras respectively. Importantly, charge alterations to conserved surfaces of cofilin that do not interfere with its actin regulatory activity leads to a dramatic increase in respiratory function that triggers a retrograde signal to up-regulate a battery of ABC transporters and concurrent metabolic changes that support multi-drug resistance. We hypothesise that cofilin functions within a novel bio-sensing system that connects the cytoskeleton and mitochondrial function to environmental challenge.<\/jats:p>","DOI":"10.1242\/jcs.099390","type":"journal-article","created":{"date-parts":[[2012,2,18]],"date-time":"2012-02-18T01:57:33Z","timestamp":1329530253000},"source":"Crossref","is-referenced-by-count":20,"title":["Identification of new surfaces of Cofilin that link mitochondrial function to the control of multi-drug resistance"],"prefix":"10.1242","author":[{"given":"Vassilios N.","family":"Kotiadis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Leadsham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Bastow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Gheeraert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennafer M","family":"Whybrew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pekka","family":"Lappalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Campbell W.","family":"Gourlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2021042522060145300_R1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1086\/510402","article-title":"Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2","volume":"80","author":"Agrawal","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2021042522060145300_R2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.2174\/138920009788898019","article-title":"Amphotericin B and its new derivatives - mode of action","volume":"10","author":"Baginski","year":"2009","journal-title":"Curr. Drug Metab."},{"key":"2021042522060145300_R3","doi-asserted-by":"crossref","first-page":"C828","DOI":"10.1152\/ajpcell.00066.2006","article-title":"Formation of actin-ADF\/cofilin rods transiently retards decline of mitochondrial potential and ATP in stressed neurons","volume":"291","author":"Bernstein","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2021042522060145300_R4","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1042\/bj1620575","article-title":"Studies of energy-linked reactions. Localization of the site of action of trialkyltin in yeast mitochondria","volume":"162","author":"Cain","year":"1977","journal-title":"Biochem. J."},{"key":"2021042522060145300_R5","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1002\/cncr.25125","article-title":"CFL1 expression levels as a prognostic and drug resistance marker in nonsmall cell lung cancer","volume":"116","author":"Castro","year":"2010","journal-title":"Cancer"},{"key":"2021042522060145300_R6","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1074\/jbc.M109.019570","article-title":"Reactive oxygen species-mediated regulation of mitochondrial biogenesis in the yeast Saccharomyces cerevisiae","volume":"285","author":"Chevtzoff","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2021042522060145300_R7","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/ncb1070","article-title":"Mitochondrial translocation of cofilin is an early step in apoptosis induction","volume":"5","author":"Chua","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"2021042522060145300_R8","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1146\/annurev-biophys-042910-155359","article-title":"Actin structure and function","volume":"40","author":"Dominguez","year":"2011","journal-title":"Annu. Rev. Biophys."},{"key":"2021042522060145300_R9","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1091\/mbc.9.2.523","article-title":"Genetic separation of FK506 susceptibility and drug transport in the yeast Pdr5 ATP-binding cassette multidrug resistance transporter","volume":"9","author":"Egner","year":"1998","journal-title":"Mol. Biol. Cell"},{"key":"2021042522060145300_R10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/cm.20516","article-title":"Diverse protective roles of the actin cytoskeleton during oxidative stress","volume":"68","author":"Farah","year":"2011","journal-title":"Cytoskeleton (Hoboken)"},{"key":"2021042522060145300_R11","doi-asserted-by":"crossref","first-page":"6487","DOI":"10.1128\/MCB.00117-06","article-title":"Actin-induced hyperactivation of the Ras signaling pathway leads to apoptosis in Saccharomyces cerevisiae","volume":"26","author":"Gourlay","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"2021042522060145300_R12","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1083\/jcb.200310148","article-title":"A role for the actin cytoskeleton in cell death and aging in yeast","volume":"164","author":"Gourlay","year":"2004","journal-title":"J. Cell Biol."},{"key":"2021042522060145300_R13","doi-asserted-by":"crossref","first-page":"37347","DOI":"10.1074\/jbc.M007338200","article-title":"Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae","volume":"275","author":"Hallstrom","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021042522060145300_R14","doi-asserted-by":"crossref","first-page":"9985","DOI":"10.1021\/bi00089a014","article-title":"Human actin depolymerizing factor mediates a pH-sensitive destruction of actin filaments","volume":"32","author":"Hawkins","year":"1993","journal-title":"Biochemistry"},{"key":"2021042522060145300_R15","doi-asserted-by":"crossref","first-page":"9994","DOI":"10.1021\/bi00089a015","article-title":"Analysis of the interactions of actin depolymerizing factor with G- and F-actin","volume":"32","author":"Hayden","year":"1993","journal-title":"Biochemistry"},{"key":"2021042522060145300_R16","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0891-5849(99)00266-X","article-title":"Oxidative stress during aging of stationary cultures of the yeast Saccharomyces cerevisiae","volume":"28","author":"Jakubowski","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"2021042522060145300_R17","first-page":"201","article-title":"A rapid permeabilization procedure for accurate quantitative determination of beta-galactosidase activity in yeast cells","volume":"128","author":"Kippert","year":"1995","journal-title":"FEMS Microbiol. Lett."},{"key":"2021042522060145300_R18","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/ncb1968","article-title":"Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin","volume":"11","author":"Klamt","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"2021042522060145300_R19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/40418","article-title":"Cofilin promotes rapid actin filament turnover in vivo","volume":"388","author":"Lappalainen","year":"1997","journal-title":"Nature"},{"key":"2021042522060145300_R20","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.1093\/emboj\/16.18.5520","article-title":"Essential functions and actin-binding surfaces of yeast cofilin revealed by systematic mutagenesis","volume":"16","author":"Lappalainen","year":"1997","journal-title":"EMBO J."},{"key":"2021042522060145300_R21","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1099\/mic.0.26742-0","article-title":"Overexpression of HAP4 in glucose-derepressed yeast cells reveals respiratory control of glucose-regulated genes","volume":"150","author":"Lascaris","year":"2004","journal-title":"Microbiology"},{"key":"2021042522060145300_R22","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/1471-2121-11-92","article-title":"cAMP\/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation","volume":"11","author":"Leadsham","year":"2010","journal-title":"BMC Cell Biol."},{"key":"2021042522060145300_R23","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1242\/jcs.042424","article-title":"Whi2p links nutritional sensing to actin-dependent Ras-cAMP-PKA regulation and apoptosis in yeast","volume":"122","author":"Leadsham","year":"2009","journal-title":"J. Cell Sci."},{"key":"2021042522060145300_R24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/genetics\/125.1.13","article-title":"Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces","volume":"125","author":"Leppert","year":"1990","journal-title":"Genetics"},{"key":"2021042522060145300_R25","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1242\/jcs.065698","article-title":"Overlapping and distinct functions for cofilin, coronin and Aip1 in actin dynamics in vivo","volume":"123","author":"Lin","year":"2010","journal-title":"J. Cell Sci."},{"key":"2021042522060145300_R26","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1046\/j.1432-1327.1998.2560388.x","article-title":"The effect of two actin depolymerizing factors (ADF\/cofilins) on actin filament turnover: pH sensitivity of F-actin binding by human ADF, but not of Acanthamoeba actophorin","volume":"256","author":"Maciver","year":"1998","journal-title":"Eur. J. Biochem."},{"key":"2021042522060145300_R27","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/35023579","article-title":"Neurodegenerative stimuli induce persistent ADF\/cofilin-actin rods that disrupt distal neurite function","volume":"2","author":"Minamide","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"2021042522060145300_R28","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1091\/mbc.10.5.1325","article-title":"Crosstalk between the Ras2p-controlled mitogen-activated protein kinase and cAMP pathways during invasive growth of Saccharomyces cerevisiae","volume":"10","author":"M\u00f6sch","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"2021042522060145300_R29","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s00432-011-1001-5","article-title":"Validation of cofilin-1 as a biomarker in non-small cell lung cancer: application of quantitative method in a retrospective cohort","volume":"137","author":"M\u00fcller","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"2021042522060145300_R30","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/embor.2009.58","article-title":"Regulation of actin function by protein kinase A-mediated phosphorylation of Limk1","volume":"10","author":"Nadella","year":"2009","journal-title":"EMBO Rep."},{"key":"2021042522060145300_R31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4161\/nucl.14508","article-title":"The F-actin severing protein cofilin-1 is required for RNA polymerase II transcription elongation","volume":"2","author":"Obrdlik","year":"2011","journal-title":"Nucleus"},{"key":"2021042522060145300_R32","doi-asserted-by":"crossref","first-page":"15562","DOI":"10.1021\/bi0117697","article-title":"Identification of yeast cofilin residues specific for actin monomer and PIP2 binding","volume":"40","author":"Ojala","year":"2001","journal-title":"Biochemistry"},{"key":"2021042522060145300_R33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1006\/jmbi.2000.3688","article-title":"Uncoupling actin filament fragmentation by cofilin from increased subunit turnover","volume":"298","author":"Pope","year":"2000","journal-title":"J. Mol. Biol."},{"key":"2021042522060145300_R34","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/j.1471-4159.2011.07599.x","article-title":"Cofilin activation mediates Bax translocation to mitochondria during excitotoxic neuronal death","volume":"120","author":"Posadas","year":"2012","journal-title":"J. Neurochem."},{"key":"2021042522060145300_R35","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.cellsig.2010.10.025","article-title":"Removal or masking of phosphatidylinositol(4,5)bisphosphate from the outer mitochondrial membrane causes mitochondrial fragmentation","volume":"23","author":"Rosivatz","year":"2011","journal-title":"Cell. Signal."},{"key":"2021042522060145300_R36","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.bbapap.2008.12.012","article-title":"Coordinate control of lipid composition and drug transport activities is required for normal multidrug resistance in fungi","volume":"1794","author":"Shahi","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"2021042522060145300_R37","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.ejcb.2008.04.001","article-title":"Ins and outs of ADF\/cofilin activity and regulation","volume":"87","author":"Van Troys","year":"2008","journal-title":"Eur. J. Cell Biol."},{"key":"2021042522060145300_R38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3109\/10408418709104448","article-title":"Anti-Candida drugs--the biochemical basis for their activity","volume":"15","author":"Vanden Bossche","year":"1987","journal-title":"Crit. Rev. Microbiol."},{"key":"2021042522060145300_R39","doi-asserted-by":"crossref","first-page":"e1078","DOI":"10.1371\/journal.pone.0001078","article-title":"Optimized protein extraction for quantitative proteomics of yeasts","volume":"2","author":"von der Haar","year":"2007","journal-title":"PLoS ONE"},{"key":"2021042522060145300_R40","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/1097-0061(200011)16:15<1421::AID-YEA624>3.0.CO;2-U","article-title":"Mitochondria-targeted green fluorescent proteins: convenient tools for the study of organelle biogenesis in Saccharomyces cerevisiae","volume":"16","author":"Westermann","year":"2000","journal-title":"Yeast"},{"key":"2021042522060145300_R41","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0014-5793(93)81071-7","article-title":"The pde2 gene of Saccharomyces cerevisiae is allelic to rca1 and encodes a phosphodiesterase which protects the cell from extracellular cAMP","volume":"325","author":"Wilson","year":"1993","journal-title":"FEBS Lett."},{"key":"2021042522060145300_R42","doi-asserted-by":"crossref","first-page":"38047","DOI":"10.1074\/jbc.M502849200","article-title":"Cytotoxicity of an anti-cancer lysophospholipid through selective modification of lipid raft composition","volume":"280","author":"Zaremberg","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021042522060145300_R43","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1016\/j.bpj.2010.01.046","article-title":"ADF\/cofilin binds phosphoinositides in a multivalent manner to act as a PIP(2)-density sensor","volume":"98","author":"Zhao","year":"2010","journal-title":"Biophys. J."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/125\/9\/2288\/1957171\/2288.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.099390\/2006791\/jcs099390.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.099390\/2006791\/jcs099390.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T21:09:00Z","timestamp":1621372140000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/doi\/10.1242\/jcs.099390\/258350\/Identification-of-new-surfaces-of-Cofilin-that"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,1]]},"references-count":43,"URL":"https:\/\/doi.org\/10.1242\/jcs.099390","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2012,1,1]]},"article-number":"jcs.099390"}}