title: Alternative oxidase dependent respiration leads to an increased mitochondrial content in two long-lived mutants of the aging model Podospora anserina.
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 grisea and PaCox17::ble contain elevated levels of mitochondrial proteins involved in quality control, i. e. LON protease and the molecular chaperone HSP60. Taken together, our work demonstrates that AOX-dependent respiration in two mutants of the ageing model P. anserina is linked to a novel mechanism involved in the retrograde response pathway, mitochondrial biogenesis, which might also play an important role for cellular maintenance in other organisms.
authors.affiliation: Faculty for Biosciences, Molecular Developmental Biology, Cluster of Excellence Macromolecular Complexes, Johann Wolfgang Goethe University, Frankfurt, Germany. scheckhuber@bio.uni-frankfurt.de
authors.forename: Christian Q
authors.initials: CQ
authors.lastname: Scheckhuber
authors.forename: Koen
authors.initials: K
authors.lastname: Houthoofd
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Weil
authors.forename: Alexandra
authors.initials: A
authors.lastname: Werner
authors.forename: Annemie
authors.initials: A
authors.lastname: De Vreese
authors.forename: Jacques R
authors.initials: JR
authors.lastname: Vanfleteren
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D004734:Energy Metabolism; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010101:Oxygen Consumption; D010940:Plant Proteins / Q000378:metabolism*; D048468:Podospora / Q000201:enzymology* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000099188:Alternative Oxidase
chemical_list: D000255:Adenosine Triphosphate; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D000099188:Alternative Oxidase