Ablation of cellular prion protein expression affects mitochondrial numbers and morphology.
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.
Miele
Gino
G
Department of Gene Expression and Development, Roslin Institute, Roslin, Midlothian, Scotland, United Kingdom.
Jeffrey
Martin
M
Turnbull
Doug
D
Manson
Jean
J
Clinton
Michael
M
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
D000682:Amyloid; D018621:PrPC Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors; D013482:Superoxide Dismutase