Department of Biological Sciences, University of Alberta, Alberta, Canada.
Mol Biol Cell. 2010 May 15;21(10):1725-36. doi: 10.1091/mbc.e09-10-0844. Epub 2010 Mar 24.
The Mdm10, Mdm12, and Mmm1 proteins have been implicated in several mitochondrial functions including mitochondrial distribution and morphology, assembly of beta-barrel proteins such as Tom40 and porin, association of mitochondria and endoplasmic reticulum, and maintaining lipid composition of mitochondrial membranes. Here we show that loss of any of these three proteins in Neurospora crassa results in the formation of large mitochondrial tubules and reduces the assembly of porin and Tom40 into the outer membrane. We have also investigated the relationship of Mdm10 and Tom7 in the biogenesis of beta-barrel proteins. Previous work showed that mitochondria lacking Tom7 assemble Tom40 more efficiently, and porin less efficiently, than wild-type mitochondria. Analysis of mdm10 and tom7 single and double mutants, has demonstrated that the effects of the two mutations are additive. Loss of Tom7 partially compensates for the decrease in Tom40 assembly resulting from loss of Mdm10, whereas porin assembly is more severely reduced in the double mutant than in either single mutant. The additive effects observed in the double mutant suggest that different steps in beta-barrel assembly are affected in the individual mutants. Many aspects of Tom7 and Mdm10 function in N. crassa are different from those of their homologues in Saccharomyces cerevisiae.
Mdm10、Mdm12 和 Mmm1 蛋白参与多种线粒体功能，包括线粒体分布和形态、β-桶蛋白（如 Tom40 和 porin）的组装、线粒体和内质网的关联以及维持线粒体膜的脂质组成。在这里，我们发现 Neurospora crassa 中这三种蛋白的任何一种缺失都会导致大的线粒体小管形成，并减少 porin 和 Tom40 组装到外膜中。我们还研究了 Mdm10 和 Tom7 在β-桶蛋白生物发生中的关系。以前的工作表明，缺乏 Tom7 的线粒体比野生型线粒体更有效地组装 Tom40，但组装 porin 的效率较低。对 mdm10 和 tom7 单突变体和双突变体的分析表明，这两种突变的影响是累加的。Tom7 的缺失部分补偿了因 Mdm10 缺失而导致的 Tom40 组装减少，而在双突变体中，porin 的组装比在任何一个单突变体中都严重减少。在双突变体中观察到的累加效应表明，在单个突变体中，β-桶组装的不同步骤受到影响。Tom7 和 Mdm10 在 N. crassa 中的许多功能与它们在酿酒酵母中的同源物不同。
