{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:14:26Z","timestamp":1792790066479,"version":"4.5.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,9,2]]},"abstract":"<jats:p>\n                    Manganese-containing superoxide dismutase (SOD2) plays a critical role in\n guarding against mitochondrial oxidative stress and is essential for survival\n of many organisms. Despite the recognized importance of SOD2, nothing is known\n regarding the mechanisms by which this nuclear-encoded protein is converted to\n an active enzyme in the mitochondrial matrix. To search for factors that\n participate in the posttranslational activation of SOD2, we screened for yeast\n genes that when mutated lead to SOD2 inactivation and identified a single ORF,\n                    <jats:italic>YGR257c<\/jats:italic>\n                    . The encoded protein localizes to the mitochondria and\n represents a member of the yeast mitochondrial carrier family.\n                    <jats:italic>YGR257c<\/jats:italic>\n                    was previously recognized as the homologue to human CGI-69, a\n widely expressed mitochondrial carrier family of unknown function. Our studies\n suggest a connection with SOD2, and we have named the yeast gene\n                    <jats:italic>MTM1<\/jats:italic>\n                    for manganese trafficking factor for mitochondrial SOD2. Inactivation of yeast\n                    <jats:italic>MTM1<\/jats:italic>\n                    leads to loss of SOD2 activity that is restored only when cells\n are treated with high supplements of manganese, but not other heavy metals,\n indicative of manganese deficiency in the SOD2 polypeptide. Surprisingly, the\n mitochondrial organelle of\n                    <jats:italic>mtm1<\/jats:italic>\n                    \u0394 mutants shows no deficiency in\n manganese levels. Moreover,\n                    <jats:italic>mtm1<\/jats:italic>\n                    \u0394 mutations do not impair\n activity of a cytosolic version of manganese SOD. We propose that Mtm1p\n functions in the mitochondrial activation of SOD2 by specifically facilitating\n insertion of the essential manganese cofactor.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1632471100","type":"journal-article","created":{"date-parts":[[2003,9,2]],"date-time":"2003-09-02T13:27:00Z","timestamp":1062509220000},"page":"10353-10357","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":141,"title":["Manganese activation of superoxide dismutase 2 in\n                    <i>Saccharomyces cerevisiae<\/i>\n                    requires\n                    <i>MTM1<\/i>\n                    , a member of the mitochondrial carrier family"],"prefix":"10.1073","volume":"100","author":[{"given":"Edward","family":"Luk","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology\r and Division of Toxicological Sciences,\r Department of Environmental Health Sciences, Bloomberg School of Public\r Health, The Johns Hopkins University, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology\r and Division of Toxicological Sciences,\r Department of Environmental Health Sciences, Bloomberg School of Public\r Health, The Johns Hopkins University, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology\r and Division of Toxicological Sciences,\r Department of Environmental Health Sciences, Bloomberg School of Public\r Health, The Johns Hopkins University, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria Cizewski","family":"Culotta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology\r and Division of Toxicological Sciences,\r Department of Environmental Health Sciences, Bloomberg School of Public\r Health, The Johns Hopkins University, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,7,30]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9782"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-376"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.3.846"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252342899"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90270-M"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47769-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.38.23469"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.805"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004380100482"},{"key":"e_1_3_2_10_2","first-page":"227","volume":"20","year":"1999","unstructured":"Pal, P. 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