{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:14:17Z","timestamp":1789420457537,"version":"build-2803163510"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"FIS-ISCIII","award":["PI01199.12"],"award-info":[{"award-number":["PI01199.12"]}]},{"name":"FIS-ISCIII","award":["PI01455.13"],"award-info":[{"award-number":["PI01455.13"]}]},{"name":"FIS-ISCIII","award":["PI01738.13"],"award-info":[{"award-number":["PI01738.13"]}]},{"name":"FIS-ISCIII","award":["PI00005.14"],"award-info":[{"award-number":["PI00005.14"]}]},{"name":"FIS-ISCIII","award":["PI00817.15"],"award-info":[{"award-number":["PI00817.15"]}]},{"name":"FIS-ISCIII","award":["PI00903.15"],"award-info":[{"award-number":["PI00903.15"]}]},{"name":"CIBERER, INTERCIBER-ISCIII, and FEDER","award":["PIE1400061"],"award-info":[{"award-number":["PIE1400061"]}]},{"name":"Suports a Grups de Recerca and CERCA Programme de la Generalitat de Catalunya","award":["2014\/SGR\/376"],"award-info":[{"award-number":["2014\/SGR\/376"]}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de TV3","doi-asserted-by":"crossref","award":["87\/C\/2015"],"award-info":[{"award-number":["87\/C\/2015"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fundaci\u00f3 Cellex","award":["IP42019"],"award-info":[{"award-number":["IP42019"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>The antibiotic linezolid is a ribosomal inhibitor with excellent efficacy. Although the administration period has been reduced to 28 days, side effects, usually of hematologic or neuropathic origin, are still reported due to secondary inhibition of mitochondrial protein synthesis. Susceptibility to linezolid toxicity remains unknown. Therefore, the objective of this study was to gain an understanding of clinical heterogeneity in response to identical linezolid exposures through exhaustive examination of the molecular basis of tissue-dependent mitotoxicity, consequent cell dysfunction, and the association of mitochondrial genetics with adverse effects of linezolid administered for the recommended period. Peripheral blood mononuclear cells (PBMC) and skin nerve fibers from 19 and 6 patients, respectively, were evaluated before and after a 28-day linezolid treatment in order to assess toxic effects on mitochondria and cells. Mitochondrial DNA haplotypes and single nucleotide polymorphisms (SNPs) in ribosomal sequences where linezolid binds to mitochondrial ribosomes were also analyzed to investigate their genetic contributions. We found that linezolid reduced mitochondrial protein levels, complex IV activity, and mitochondrial mass in PBMC and was associated with a trend toward an increase in the rate of apoptosis. In skin tissue, mitochondrial mass increased within nerve fibers, accompanied by subclinical axonal swelling. Mitochondrial haplogroup U, mutations in 12S rRNA, and the m.2706A\u2192G, m.3197T\u2192C, and m.3010G\u2192A polymorphisms in 16S rRNA showed a trend toward an association with increased mitochondrial and clinical adverse effects. We conclude that even when linezolid is administered for a shorter time than formerly, adverse effects are reported by 63% of patients. Linezolid exerts tissue-dependent mitotoxicity that is responsible for downstream cellular consequences (blood cell death and nerve fiber swelling), leading to adverse hematologic and peripheral nervous side effects. Multicentric studies should confirm genetic susceptibility in larger cohorts.<\/jats:p>","DOI":"10.1128\/aac.00542-17","type":"journal-article","created":{"date-parts":[[2017,7,4]],"date-time":"2017-07-04T00:40:52Z","timestamp":1499128852000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Influence of Mitochondrial Genetics on the Mitochondrial Toxicity of Linezolid in Blood Cells and Skin Nerve Fibers"],"prefix":"10.1128","volume":"61","author":[{"given":"G.","family":"Garrabou","sequence":"first","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Sciences\u2014University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-0811","authenticated-orcid":false,"given":"\u00c0.","family":"Soriano","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital Clinic of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Pin\u00f3s","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"},{"name":"Mitochondrial and Neuromuscular Pathology Department, CIBBIM, Laboratory, Institute of Research, Hospital Universitari Vall d'Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Casanova-Moll\u00e0","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Clinic of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Pacheu-Grau","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"},{"name":"Biochemical, Molecular and Cellular Biology Department, University of Zaragoza, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Mor\u00e9n","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Sciences\u2014University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Garc\u00eda-Arum\u00ed","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"},{"name":"Mitochondrial and Neuromuscular Pathology Department, CIBBIM, Laboratory, Institute of Research, Hospital Universitari Vall d'Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Morales","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Clinic of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Ruiz-Pesini","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"},{"name":"Biochemical, Molecular and Cellular Biology Department, University of Zaragoza, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Catal\u00e1n-Garcia","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Sciences\u2014University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"Milisenda","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Sciences\u2014University of Barcelona, Barcelona, Spain"},{"name":"Internal Medicine Department, Hospital Clinic of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Lozano","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Sciences\u2014University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. L.","family":"Andreu","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"},{"name":"Mitochondrial and Neuromuscular Pathology Department, CIBBIM, Laboratory, Institute of Research, Hospital Universitari Vall d'Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Montoya","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"},{"name":"Biochemical, Molecular and Cellular Biology Department, University of Zaragoza, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Mensa","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Hospital Clinic of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Cardellach","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Sciences\u2014University of Barcelona, Barcelona, Spain"},{"name":"Internal Medicine Department, Hospital Clinic of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras\u2021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804276105"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-138-2-200301210-00015"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200301023480123"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.11.1010.34517"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1C361"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/340982"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh199"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/422147"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/379012"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)01109-0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh405"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/430441"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200511243532123"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/501356"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01411-05"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3896-3902.2005"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e3181b1ed42"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2011.08.010"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01190-06"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3182186035"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00396.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133130"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.10.008"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.10.115"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01819-09"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds517"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1201964"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(88)90013-8"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)46988-8"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000070781.92512.A4"},{"key":"e_1_3_3_32_2","first-page":"37","article-title":"Mitochondrial lineages distribution in the Spanish population: anticipating association studies","volume":"72","author":"Dahmany Y","year":"2006","unstructured":"Dahmany Y MarcuelloA Montiel-SosaFJ MontoyaJ D\u00edez-SanchezC L\u00f3pez-P\u00e9rezMJ Ruiz-PesiniE. 2006. Mitochondrial lineages distribution in the Spanish population: anticipating association studies. Anales Real Acad Nac Farm72:37\u201344.","journal-title":"Anales Real Acad Nac Farm"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.5.771"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02856-14"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir764"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90647-2"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00729-05"},{"key":"e_1_3_3_38_2","first-page":"20","article-title":"A method of separating mononuclears on a density gradient","volume":"1990","author":"Prilutskii AS","year":"1990","unstructured":"Prilutskii AS KhodakovskiiAV MailianEA. 1990. A method of separating mononuclears on a density gradient. Lab Delo1990(2):20\u201323. (In Russian.)","journal-title":"Lab Delo"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(94)90055-8"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(93)90223-L"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.45.10.1848"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2008.03096.x"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00269.x"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc11150"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00542-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00542-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:55:20Z","timestamp":1645476920000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00542-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1128\/AAC.00542-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00542-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9]]},"assertion":[{"value":"2017-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00542-17"}}