title: Simultaneous impairment of mitochondrial fission and fusion reduces mitophagy and shortens replicative lifespan.
abstract: Aging of biological systems is accompanied by degeneration of mitochondrial functions. Different pathways are active to counteract the processes which lead to mitochondrial dysfunction. Mitochondrial dynamics, the fission and fusion of mitochondria, is one of these quality control pathways. Mitophagy, the controlled degradation of mitochondria, is another one. Here we show that these pathways are linked. A double deletion mutant of Saccharomyces cerevisiae in which two essential components of the fission and fusion machinery, Dnm1 and Mgm1, are simultaneously ablated, contain wild-type like filamentous mitochondria, but are characterized by impaired respiration, an increased sensitivity to different stressors, increased mitochondrial protein carbonylation, and a decrease in mitophagy and replicative lifespan. These data show that a balanced mitochondrial dynamics and not a filamentous mitochondrial morphotype per se is the key for a long lifespan and demonstrate a cross-talk between two different mitochondrial quality control pathways.
authors.affiliation: 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: Dominik
authors.initials: D
authors.lastname: Bernhardt
authors.affiliation: Mitochondrial Biology, Buchmann Institute for Molecular Life Sciences &Zentrum für Molekulare Medizin, Goethe University, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Müller
authors.affiliation: 1] Mitochondrial Biology, Buchmann Institute for Molecular Life Sciences &Zentrum für Molekulare Medizin, Goethe University, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany [2] Heinrich-Heine Universität, Universitätsklinikum Düsseldorf, Institut für Biochemie und Molekularbiologie I, Universitätsstr. 1, 40225 Düsseldorf.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Reichert
authors.affiliation: 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: D001343:Autophagy / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D063306:Mitophagy / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: C082883:MGM1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C094774:DNM1 protein, S cerevisiae