Manganese activation of superoxide dismutase 2 in Saccharomyces cerevisiae requires MTM1, a member of the mitochondrial carrier family
Manganese activation of superoxide dismutase 2 in Saccharomyces cerevisiae requires MTM1, a member of the mitochondrial carrier family
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DOI：
10.1073/pnas.1632471100
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发表时间：
2003-09-02
影响因子：
11.1
通讯作者：
Culotta, VC
中科院分区：
文献类型：
--
作者：
Luk, E;Carroll, M;Culotta, VC
含锰超氧化物歧化酶（SOD 2）在抵御线粒体氧化应激中起着关键作用，对许多生物的生存至关重要。尽管SOD 2的重要性已被公认，但关于这种核编码蛋白在线粒体基质中转化为活性酶的机制尚不清楚。为了寻找参与SOD 2翻译后激活的因素，我们筛选了突变时导致SOD 2失活的酵母基因，并确定了一个单一的ORF，YGR 257 c。编码的蛋白定位于线粒体，代表酵母线粒体载体家族的成员。YGR 257 c以前被认为是人类CGI-69的同源物，CGI-69是一种广泛表达的功能未知的线粒体载体家族。我们的研究表明与SOD 2的连接，我们命名为线粒体SOD 2锰运输因子的酵母基因MTM 1。酵母MTM 1的失活导致SOD 2活性的丧失，仅当细胞用高补充的锰而不是其他重金属处理时才恢复，这表明SOD 2多肽中缺乏锰。令人惊讶的是，mtm 1Delta突变体的线粒体细胞器显示锰水平没有缺乏。此外，mtm 1Delta突变不损害锰SOD的胞质版本的活性。我们建议，Mtm 1 p的功能，特别是促进插入的必需锰辅因子在线粒体激活的SOD 2。
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 mtm1Delta mutants shows no deficiency in manganese levels. Moreover, mtm1Delta 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.