title: A systems biological analysis links ROS metabolism to mitochondrial protein quality control.
abstract: The analyses of previously generated Podospora anserina strains in which the mitochondrial superoxide dismutase, PaSOD3, is increased in abundance, revealed unexpected results, which, at first glance, are contradictory to the 'free radical theory of aging' (FRTA). To re-analyze these results, we performed additional experiments and developed a mathematical model consisting of a set of differential equations describing the time course of various ROS (reactive oxygen species), components of the cellular antioxidant system (PaSOD3 and mitochondrial peroxiredoxin, PaPRX1), and PaCLPP, a mitochondrial matrix protease involved in protein quality control. Incorporating these components we could identify a positive feed-back loop and demonstrate that the role of superoxide as the primary ROS responsible for age-related molecular damage is more complicated than originally stated by the FRTA. Our study is a first step towards the integration of the various pathways known to be involved in the control of biological aging.
authors.affiliation: Humboldt-Universität zu Berlin, Institute for Biology, Theoretical Biophysics, Invalidenstrasse 42, 10115 Berlin, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Kowald
authors.forename: Andrea
authors.initials: A
authors.lastname: Hamann
authors.forename: Sandra
authors.initials: S
authors.lastname: Zintel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ullrich
authors.forename: Edda
authors.initials: E
authors.lastname: Klipp
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
mesh_terms: D000375:Aging / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D048468:Podospora / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D049490:Systems Biology
chemical_list: D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase