Wild-type filamentous fungus Neurospora crassa continues to grow its hyphae for a very lengthy period of time (>2 years), whereas mutations at the natural death (nd) locus shorten life span (approximately 20 days). By positional cloning based on heat augmented mutagen sensitivity of the nd strain, we identified a nonsense mutation in the msh1 gene, an eukaryotic homolog of bacterial MutS, and this mutation resulted in encoding non-functional polypeptide. By tagging with GFP, subcellular localization of the MSH1 protein in the mitochondria was observed, and knock out of the msh1 gene caused severe growth deficiency accompanying mitochondrial DNA (mtDNA) aberrations such as large-scale mtDNA deletions and rearrangements as seen in the nd strain. These results suggested that MSH1 may maintain mtDNA integrity. Thus, loss of function compromises mtDNA, leading to the acceleration of cellular aging.

野生型丝状真菌粗糙脉孢菌在很长一段时间内（> 2 年）继续生长其菌丝，而自然死亡( nd ) 位点的突变缩短了寿命（约 20 天）。通过基于热定位克隆扩增的诱变剂的灵敏度第二应变，我们确定在一个无义突变msh1基因，细菌MutS的的真核同源物，并且这突变导致编码非功能性多肽。通过用 GFP 标记，观察到 MSH1 蛋白在线粒体中的亚细胞定位，并敲除msh1基因导致严重的生长缺陷，伴随着线粒体 DNA (mtDNA) 畸变，如nd菌株中所见的大规模 mtDNA 缺失和重排。这些结果表明 MSH1 可能保持 mtDNA 的完整性。因此，功能丧失会损害 mtDNA，导致细胞衰老加速。