title: RCF1-dependent respiratory supercomplexes are integral for lifespan-maintenance in a fungal ageing model.
abstract: Mitochondrial respiratory supercomplexes (mtRSCs) are stoichiometric assemblies of electron transport chain (ETC) complexes in the inner mitochondrial membrane. They are hypothesized to regulate electron flow, the generation of reactive oxygen species (ROS) and to stabilize ETC complexes. Using the fungal ageing model Podospora anserina, we investigated the impact of homologues of the Saccharomyces cerevisiae respiratory supercomplex factors 1 and 2 (termed PaRCF1 and PaRCF2) on mtRSC formation, fitness and lifespan. Whereas PaRCF2's role seems negligible, ablation of PaRCF1 alters size of monomeric complex IV, reduces the abundance of complex IV-containing supercomplexes, negatively affects vital functions and shortens lifespan. PaRcf1 overexpression slightly prolongs lifespan, though without appreciably influencing ETC organization. Overall, our results identify PaRCF1 as necessary yet not sufficient for mtRSC formation and demonstrate that PaRCF1-dependent stability of complex IV and associated supercomplexes is highly relevant for maintenance of the healthy lifespan in a eukaryotic model organism.
authors.affiliation: Johann Wolfgang Goethe University, Faculty for Biosciences &Cluster of Excellence 'Macromolecular Complexes' Frankfurt, Institute of Molecular Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Fischer
authors.affiliation: Johann Wolfgang Goethe University, Faculty for Biosciences &Cluster of Excellence 'Macromolecular Complexes' Frankfurt, Institute of Molecular Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Filippis
authors.affiliation: Johann Wolfgang Goethe University, Faculty for Biosciences &Cluster of Excellence 'Macromolecular Complexes' Frankfurt, Institute of Molecular Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D015153:Blotting, Western; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D048468:Podospora / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV