Sellem Carole H, Lemaire Claire, Lorin Séverine, Dujardin Geneviève, Sainsard-Chanet Annie
Centre de Génétique Moléculaire UPR 2167, Associated with the University of Paris-Sud 11 CNRS, Gif-sur-Yvette, France.
Genetics. 2005 Mar;169(3):1379-89. doi: 10.1534/genetics.104.033837. Epub 2004 Nov 15.
A causal link between deficiency of the cytochrome respiratory pathway and life span was previously shown in the filamentous fungus Podospora anserina. To gain more insight into the relationship between mitochondrial function and life span, we have constructed a strain carrying a thermosensitive mutation of the gene oxa1. OXA1 is a membrane protein conserved from bacteria to human. The mitochondrial OXA1 protein is involved in the assembly/insertion of several respiratory complexes. We show here that oxa1 is an essential gene in P. anserina. The oxa1(ts) mutant exhibits severe defects in the respiratory complexes I and IV, which are correlated with an increased life span, a strong induction of the alternative oxidase, and a reduction in ROS production. However, there is no causal link between alternative oxidase level and life span. We also show that in the oxa1(ts) mutant, the extent of the defects in complexes I and IV and the life-span increase depends on the essential gene rmp1. The RMP1 protein, whose function is still unknown, can be localized in the mitochondria and/or the cytosolic compartment, depending on the developmental stage. We propose that the RMP1 protein could be involved in the process of OXA1-dependent protein insertion.
细胞色素呼吸途径缺陷与寿命之间的因果联系先前已在丝状真菌嗜热栖热菌中得到证实。为了更深入地了解线粒体功能与寿命之间的关系，我们构建了一个携带oxa1基因热敏突变的菌株。OXA1是一种从细菌到人类都保守的膜蛋白。线粒体OXA1蛋白参与多种呼吸复合体的组装/插入。我们在此表明，oxa1是嗜热栖热菌中的一个必需基因。oxa1(ts)突变体在呼吸复合体I和IV中表现出严重缺陷，这与寿命延长、交替氧化酶的强烈诱导以及活性氧产生的减少相关。然而，交替氧化酶水平与寿命之间没有因果联系。我们还表明，在oxa1(ts)突变体中，复合体I和IV中的缺陷程度以及寿命延长取决于必需基因rmp1。RMP1蛋白的功能仍然未知，根据发育阶段，它可以定位于线粒体和/或胞质区室。我们提出，RMP1蛋白可能参与OXA1依赖性蛋白插入过程。
