title: Ablation of cellular prion protein expression affects mitochondrial numbers and morphology.
abstract: The cellular prion protein (PrP(C)), predominantly expressed in the central nervous system, is required for pathogenesis of prion neurodegenerative diseases and its conversion into a pathogenic isoform (PrP(Sc)) is a common feature of disease. While the physiological function of PrP(C) remains unclear, accumulating evidence indicates a role for PrP(C) in oxidative homeostasis in vivo and suggests that PrP(C) may be involved in the cellular response to oxidative stress. Mice in which PrP(C) expression has been ablated are viable and develop normally. Here we show that in an inbred line of mice, in tissues that normally express PrP at moderate to high levels, ablation of PrP(C) results in reduced mitochondrial numbers, unusual mitochondrial morphology, and elevated levels of mitochondrial manganese-dependent superoxide dismutase antioxidant enzyme. These observations may have relevance to the pathogenic mechanism for this group of fatal neurodegenerative conditions.
authors.affiliation: Department of Gene Expression and Development, Roslin Institute, Roslin, Midlothian, Scotland, United Kingdom.
authors.forename: Gino
authors.initials: G
authors.lastname: Miele
authors.forename: Martin
authors.initials: M
authors.lastname: Jeffrey
authors.forename: Doug
authors.initials: D
authors.lastname: Turnbull
authors.forename: Jean
authors.initials: J
authors.lastname: Manson
authors.forename: Michael
authors.initials: M
authors.lastname: Clinton
mesh_terms: D000682:Amyloid / Q000235:genetics; D000818:Animals; D006624:Hippocampus / Q000201:enzymology / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure*; D008929:Mitochondria, Heart / Q000201:enzymology / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000201:enzymology / Q000648:ultrastructure; D018621:PrPC Proteins / Q000378:metabolism / Q000502:physiology*; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000682:Amyloid; D018621:PrPC Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors; D013482:Superoxide Dismutase