Mss51p and Cox14p jointly regulate mitochondrial Cox1p expression in Saccharomyces cerevisiae
Mss51p and Cox14p jointly regulate mitochondrial Cox1p expression in Saccharomyces cerevisiae
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DOI：
10.1038/sj.emboj.7600358
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发表时间：
2004-09-01
期刊：
影响因子：
11.4
通讯作者：
Tzagoloff, A
中科院分区：
文献类型：
--
作者：
Barrientos, A;Zambrano, A;Tzagoloff, A
SURF 1（酵母SHY 1的人类同源物）的突变导致Leigh综合征，这是一种与细胞色素氧化酶（考克斯）缺乏相关的神经病。以前对这种疾病的酵母模型的研究表明，突变形式的Mss 51 p，一种COX 1 mRNA的翻译激活剂，通过恢复正常合成的染色体编码的考克斯1 p亚基，部分挽救了shy 1突变体的考克斯缺陷。在这里，我们目前的证据表明，Cox 1 p合成减少，在大多数考克斯突变体，但恢复到野生型的相同mss 51突变，抑制shy 1突变。一个重要的例外是COX 14中的无效突变，其本身或与其他考克斯突变组合不影响Cox 1 p合成。Cox 14 p和Mss 51 p被证明与新合成的Cox 1 p相互作用。我们认为Mss 51 p和Cox 14 p与Cox 1 p相互作用形成一个短暂的Cox 14 p-Cox 1 p-Mss 51 p复合物，从而下调Cox 1 p的合成。Mss 51 p从复合物中的释放发生在组装途径的下游步骤，可能由Shy 1 p催化。
Mutations in SURF1, the human homologue of yeast SHY1, are responsible for Leigh's syndrome, a neuropathy associated with cytochrome oxidase (COX) deficiency. Previous studies of the yeast model of this disease showed that mutant forms of Mss51p, a translational activator of COX1 mRNA, partially rescue the COX deficiency of shy1 mutants by restoring normal synthesis of the mitochondrially encoded Cox1p subunit of COX. Here we present evidence showing that Cox1p synthesis is reduced in most COX mutants but is restored to that of wild type by the same mss51 mutation that suppresses shy1 mutants. An important exception is a null mutation in COX14, which by itself or in combination with other COX mutations does not affect Cox1p synthesis. Cox14p and Mss51p are shown to interact with newly synthesized Cox1p and with each other. We propose that the interaction of Mss51p and Cox14p with Cox1p to form a transient Cox14p-Cox1p-Mss51p complex functions to downregulate Cox1p synthesis. The release of Mss51p from the complex occurs at a downstream step in the assembly pathway, probably catalyzed by Shy1p.