alternative oxidase dependent respiration leads to an increased mitochondrial content in two long-lived mutants of the ageing model podospora anserina替代氧化酶依赖呼吸导致线粒体含量增加两个长期老化模型的突变体柄孢壳菌属anserina.pdfVIP

Alternative Oxidase Dependent Respiration Leads to an Increased Mitochondrial Content in Two Long-Lived Mutants of the Ageing Model Podospora anserina 1 2 1 1 Christian Q. Scheckhuber *, Koen Houthoofd , Andrea C. Weil , Alexandra Werner , Annemie De 2 2 1 Vreese , Jacques R. Vanfleteren , Heinz D. Osiewacz 1 Faculty for Biosciences, Molecular Developmental Biology, Cluster of Excellence Macromolecular Complexes, Johann Wolfgang Goethe University, Frankfurt, Germany, 2 Department of Biology and Center for Molecular Phylogeny and Evolution, Ghent University, Ghent, Belgium Abstract The retrograde response constitutes an important signalling pathway from mitochondria to the nucleus which induces several genes to allow compensation of mitochondrial impairments. In the filamentous ascomycete Podospora anserina, an example for such a response is the induction of a nuclear-encoded and iron-dependent alternative oxidase (AOX) occurring when cytochrome-c oxidase (COX) dependent respiration is affected. Several long-lived mutants are known which predominantly or exclusively respire via AOX. Here we show that two AOX-utilising mutants, grisea and PaCox17::ble, are able to compensate partially for lowered OXPHOS efficiency resulting from AOX-dependent respiration by increasing mitochondrial content. At the physiological level this is demonstrated by an elevated oxygen consumption and increased heat production. However, in the two mutants, ATP levels do not reach WT levels. Interestingly, mutant PaCox17::ble is characterized by a highly increased release of the reactive oxygen species (ROS) hydrogen peroxide. Both