Shepard K A, Yaffe M P
Department of Biology, University of California, San Diego, La Jolla, California 92093-0347, USA.
J Cell Biol. 1999 Feb 22;144(4):711-20. doi: 10.1083/jcb.144.4.711.
The mdm17 mutation causes temperature-dependent defects in mitochondrial inheritance, mitochondrial morphology, and the maintenance of mitochondrial DNA in the yeast Saccharomyces cerevisiae. Defects in mitochondrial transmission to daughter buds and changes in mitochondrial morphology were apparent within 30 min after shifting cells to 37 degrees C, while loss of the mitochondrial genome occurred after 4-24 h at the elevated temperature. The mdm17 lesion mapped to MGM1, a gene encoding a dynamin-like GTPase previously implicated in mitochondrial genome maintenance, and the cloned MGM1 gene complements all of the mdm17 mutant phenotypes. Cells with an mgm1-null mutation displayed aberrant mitochondrial inheritance and morphology. A version of mgm1 mutated in a conserved residue in the putative GTP-binding site was unable to complement any of the mutant defects. It also caused aberrant mitochondrial distribution and morphology when expressed at high levels in cells that also contained a wild-type copy of the gene. Mgm1p was localized to the mitochondrial outer membrane and fractionated as a component of a high molecular weight complex. These results indicate that Mgm1p is a mitochondrial inheritance and morphology component that functions on the mitochondrial surface.
mdm17突变在酿酒酵母中导致线粒体遗传、线粒体形态以及线粒体DNA维持方面的温度依赖性缺陷。将细胞转移至37摄氏度后30分钟内,线粒体向子芽的传递缺陷和线粒体形态变化就很明显,而在高温下4 - 24小时后线粒体基因组发生丢失。mdm17损伤定位于MGM1,该基因编码一种此前与线粒体基因组维持有关的发动蛋白样GTP酶,克隆的MGM1基因可弥补所有mdm17突变体表型。mgm1基因缺失突变的细胞表现出线粒体遗传和形态异常。在假定的GTP结合位点的一个保守残基处发生突变的mgm1版本无法弥补任何突变缺陷。当在也含有该基因野生型拷贝的细胞中高水平表达时,它还会导致线粒体分布和形态异常。Mgm1p定位于线粒体外膜,并作为高分子量复合物的一个组分被分离出来。这些结果表明,Mgm1p是一种在线粒体表面发挥作用的线粒体遗传和形态组分。