title: An mtDNA mutation accelerates liver aging by interfering with the ROS response and mitochondrial life cycle.
abstract: Mitochondrial dysfunction affects liver metabolism, but it remains unclear whether this interferes with normal liver aging. We investigated several mitochondrial pathways in hepatocytes and liver tissue from a conplastic mouse strain compared with the control C57BL/6NTac strain over 18 months of life. The C57BL/6NTac-mtNODLtJ mice differed from C57BL/6NTac mice by a point mutation in mitochondrial-encoded subunit 3 of cytochrome c oxidase. Young C57BL/6NTac-mtNODLtJ mice showed reduced mitochondrial metabolism but similar reactive oxygen species (ROS) production to C57BL/6NTac mice. Whereas ROS increased almost equally up to 9 months in both strains, different mitochondrial adaptation strategies resulted in decreasing ROS in advanced age in C57BL/6NTac mice, but persistent ROS production in C57BL/6NTac-mtNODLtJ mice. Only the conplastic strain developed elongated mitochondrial networks with artificial loop structures, depressed autophagy, high mitochondrial respiration and up-regulated antioxidative response. Our results indicate that mtDNA mutations accelerate liver ballooning degeneration and carry a serious risk of premature organ aging.
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Niemann
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany.
authors.forename: Cindy
authors.initials: C
authors.lastname: Johne
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schröder
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany; Institute of Nutritional Physiology "Oskar Kellner","Oskar Kellner", Leibnitz Institute for Farm Animal Biology, Dummerstorf, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Koch
authors.affiliation: Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schultz
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Tiedge
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany. Electronic address: simone.baltrusch@med.uni-rostock.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Baltrusch
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D008018:Life Cycle Stages / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: Aging; Conplastic mice; Liver; Mitochondria; Reactive oxygen species