期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：18
页码：10353-10357
DOI：10.1073/pnas.1632471100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Manganese-containing superoxide dismutase (SOD2) plays a critical role in guarding against mitochondrial oxidative stress and is essential for survival of many organisms. Despite the recognized importance of SOD2, nothing is known regarding the mechanisms by which this nuclear-encoded protein is converted to an active enzyme in the mitochondrial matrix. To search for factors that participate in the posttranslational activation of SOD2, we screened for yeast genes that when mutated lead to SOD2 inactivation and identified a single ORF, YGR257c. The encoded protein localizes to the mitochondria and represents a member of the yeast mitochondrial carrier family. YGR257c was previously recognized as the homologue to human CGI-69, a widely expressed mitochondrial carrier family of unknown function. Our studies suggest a connection with SOD2, and we have named the yeast gene MTM1 for manganese trafficking factor for mitochondrial SOD2. Inactivation of yeast MTM1 leads to loss of SOD2 activity that is restored only when cells are treated with high supplements of manganese, but not other heavy metals, indicative of manganese deficiency in the SOD2 polypeptide. Surprisingly, the mitochondrial organelle of mtm1{Delta} mutants shows no deficiency in manganese levels. Moreover, mtm1{Delta} mutations do not impair activity of a cytosolic version of manganese SOD. We propose that Mtm1p functions in the mitochondrial activation of SOD2 by specifically facilitating insertion of the essential manganese cofactor.
