The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome
The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome
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DOI：
10.1074/jbc.m403607200
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发表时间：
2004-07-16
影响因子：
4.8
通讯作者：
Schweyen, RJ
中科院分区：
文献类型：
--
作者：
Nowikovsky, K;Froschauer, EM;Schweyen, RJ
酵母开放阅读框YOL027和YPR125及其在各种真核生物中的同源物编码具有单个预测跨膜结构域的蛋白质，分子量在45至85 kDa之间。他们的人类同源LETM1的半合子缺失可能导致狼-赫施霍恩综合征表型。我们在这里表明，在酵母和人类细胞中，这些基因编码线粒体内膜的完整蛋白质。酵母YOL027基因的缺失（YOL027 δ突变）导致线粒体功能障碍。这种突变表型与酵母中人类LETM1基因的表达相辅相成，表明LETM1 /Yol027蛋白从酵母到人类的功能保存。突变体yol027Delta线粒体阳离子含量增加，特别是K+和低膜电位的DeltaPsi。在体外实验中，它们在原位大量肿胀，且对醋酸钾诱导的肿胀难以耐受，这表明它们的K+/H+交换活性存在缺陷。因此，YOL027/LETM1是第一个被发现编码参与K+稳态和细胞器体积控制的因子的基因。
The yeast open reading frames YOL027 and YPR125 and their orthologs in various eukaryotes encode proteins with a single predicted trans-membrane domain ranging in molecular mass from 45 to 85 kDa. Hemizygous deletion of their human homolog LETM1 is likely to contribute to the Wolf-Hirschhorn syndrome phenotype. We show here that in yeast and human cells, these genes encode integral proteins of the inner mitochondrial membrane. Deletion of the yeast YOL027 gene (yol027Delta mutation) results in mitochondrial dysfunction. This mutant phenotype is complemented by the expression of the human LETM1 gene in yeast, indicating a functional conservation of LetM1/Yol027 proteins from yeast to man. Mutant yol027Delta mitochondria have increased cation contents, particularly K+ and low-membrane-potential DeltaPsi. They are massively swollen in situ and refractory to potassium acetate-induced swelling in vitro, which is indicative of a defect in K+/H+ exchange activity. Thus, YOL027/LETM1 are the first genes shown to encode factors involved in both K+ homeostasis and organelle volume control.