{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:23:04Z","timestamp":1768548184197,"version":"3.49.0"},"reference-count":67,"publisher":"American Society for Cell Biology (ASCB)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:p>The inositolphosphosphingolipid phospholipase C (Isc1p) of Saccharomyces cerevisiae belongs to the family of neutral sphingomyelinases that generates the bioactive sphingolipid ceramide. In this work the role of Isc1p in oxidative stress resistance and chronological lifespan was investigated. Loss of Isc1p resulted in a higher sensitivity to hydrogen peroxide that was associated with an increase in oxidative stress markers, namely intracellular oxidation, protein carbonylation, and lipid peroxidation. Microarray analysis showed that Isc1p deficiency up-regulated the iron regulon leading to increased levels of iron, which is known to catalyze the production of the highly reactive hydroxyl radicals via the Fenton reaction. In agreement, iron chelation suppressed hydrogen peroxide sensitivity of isc1\u0394 mutants. Cells lacking Isc1p also displayed a shortened chronological lifespan associated with oxidative stress markers and aging of parental cells was correlated with a decrease in Isc1p activity. The analysis of DNA fragmentation and caspase-like activity showed that Isc1p deficiency increased apoptotic cell death associated with oxidative stress and aging. Furthermore, deletion of Yca1p metacaspase suppressed the oxidative stress sensitivity and premature aging phenotypes of isc1\u0394 mutants. These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis.<\/jats:p>","DOI":"10.1091\/mbc.e07-06-0604","type":"journal-article","created":{"date-parts":[[2007,12,28]],"date-time":"2007-12-28T01:34:19Z","timestamp":1198805659000},"page":"865-876","source":"Crossref","is-referenced-by-count":82,"title":["Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis"],"prefix":"10.1091","volume":"19","author":[{"given":"Teresa","family":"Almeida","sequence":"first","affiliation":[{"name":"*IBMC, Instituto de Biologia Molecular e Celular, Grupo de Microbiologia Celular e Aplicada, 4150-180 Porto, Portugal;"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Departamento de Biologia Molecular, Universidade do Porto, 4099-003, Porto, Portugal;"}]},{"given":"Marta","family":"Marques","sequence":"additional","affiliation":[{"name":"*IBMC, Instituto de Biologia Molecular e Celular, Grupo de Microbiologia Celular e Aplicada, 4150-180 Porto, Portugal;"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Departamento de Biologia Molecular, Universidade do Porto, 4099-003, Porto, Portugal;"}]},{"given":"Dominik","family":"Mojzita","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, G\u00f6teborg University, S-405 30 G\u00f6teborg, Sweden;"}]},{"given":"Maria A.","family":"Amorim","sequence":"additional","affiliation":[{"name":"*IBMC, Instituto de Biologia Molecular e Celular, Grupo de Microbiologia Celular e Aplicada, 4150-180 Porto, Portugal;"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Departamento de Biologia Molecular, Universidade do Porto, 4099-003, Porto, Portugal;"}]},{"given":"Rui D.","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Biologia-Centro de Biologia, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal; and"}]},{"given":"Bruno","family":"Almeida","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o em Ci\u00eancias da Vida e Sa\u00fade (ICVS), Escola de Ci\u00eancias da Sa\u00fade, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Pedro","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"*IBMC, Instituto de Biologia Molecular e Celular, Grupo de Microbiologia Celular e Aplicada, 4150-180 Porto, Portugal;"}]},{"given":"Paula","family":"Ludovico","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o em Ci\u00eancias da Vida e Sa\u00fade (ICVS), Escola de Ci\u00eancias da Sa\u00fade, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Stefan","family":"Hohmann","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, G\u00f6teborg University, S-405 30 G\u00f6teborg, Sweden;"}]},{"given":"Pedro","family":"Moradas-Ferreira","sequence":"additional","affiliation":[{"name":"*IBMC, Instituto de Biologia Molecular e Celular, Grupo de Microbiologia Celular e Aplicada, 4150-180 Porto, Portugal;"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Departamento de Biologia Molecular, Universidade do Porto, 4099-003, Porto, Portugal;"}]},{"given":"Manuela","family":"C\u00f4rte-Real","sequence":"additional","affiliation":[{"name":"Departamento de Biologia-Centro de Biologia, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal; and"}]},{"given":"V\u00edtor","family":"Costa","sequence":"additional","affiliation":[{"name":"*IBMC, Instituto de Biologia Molecular e Celular, Grupo de Microbiologia Celular e Aplicada, 4150-180 Porto, Portugal;"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Departamento de Biologia Molecular, Universidade do Porto, 4099-003, Porto, Portugal;"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/genetics\/157.3.1169","volume":"157","author":"Abramova N. 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