Cellular prion protein is present in mitochondria of healthy mice.
Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. PrPCmisfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. The precise function of PrPCremains elusive but may depend upon its cellular localization. Here we show that PrPCis present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. Mitochondrial PrPCwas fully processed with mature N-linked glycans and did not require the GPI anchor for localization. Protease treatment of purified mitochondria suggested that mitochondrial PrPCexists as a transmembrane isoform with the C-terminus facing the mitochondrial matrix and the N-terminus facing the intermembrane space. Taken together, our data suggest that PrPCcan be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPCmay affect mitochondrial function.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, National Institutes of Health, Montana 59840, USA.
Robert
R
Faris
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, National Institutes of Health, Montana 59840, USA.
Roger A
RA
Moore
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, National Institutes of Health, Montana 59840, USA.
Anne
A
Ward
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, National Institutes of Health, Montana 59840, USA.
Brent
B
Race
Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
David W
DW
Dorward
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, National Institutes of Health, Montana 59840, USA.
Jason R
JR
Hollister
Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Elizabeth R
ER
Fischer
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, National Institutes of Health, Montana 59840, USA.
Suzette A
SA
Priola
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002853:Chromatography, Liquid; D003576:Electron Transport Complex IV / Q000378:metabolism; D006031:Glycosylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism; D011485:Protein Binding; D053719:Tandem Mass Spectrometry
D011134:Polysaccharides; D018621:PrPC Proteins; D003576:Electron Transport Complex IV