Ablation of cellular prion protein expression affects mitochondrial numbers and morphology

The cellular prion protein (PrPC), predominantly expressed in the central nervous system, is required for pathogenesis of prion neurodegenerative diseases and its conversion into a pathogenic isoform. (PrPSc) is a common feature of disease. While the physiological function of PrPC remains unclear, accumulating evidence indicates a role for PrPC in oxidative homeostasis in vivo and suggests that PrPC may be involved in the cellular response to oxidative stress. Mice in which PrPC 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 PrPC 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. (C) 2002 Elsevier Science (USA).