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Updated: Mar 8, 2026
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Cellular prion protein is present in mitochondria of healthy mice
Robert Faris1, Roger A Moore1, Anne Ward1
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, National Institutes of Health, Montana 59840, USA.
Abstract:
Cellular prion protein (PrPC) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. PrPC misfolds to a pathogenic isoform PrPSc, the causative agent of neurodegenerative prion diseases. The precise function of PrPC remains elusive but may depend upon its cellular localization. Here we show that PrPC is present in brain mitochondria from 6-12 week old wild-type and transgenic mice in the absence of disease. Mitochondrial PrPC was fully processed with mature N-linked glycans and did not require the GPI anchor for localization. Protease treatment of purified mitochondria suggested that mitochondrial PrPC exists 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 PrPC can be found in mitochondria in the absence of disease, old age, mutation, or overexpression and that PrPC may affect mitochondrial function.
Insights
Cellular prion protein (PrPC) is found in brain mitochondria, independent of disease. This discovery suggests a potential role for PrPC in mitochondrial function.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Cellular prion protein (PrPC) is a glycoprotein typically anchored to the plasma membrane via a GPI anchor.
- PrPC misfolding leads to the pathogenic isoform PrPSc, causing neurodegenerative prion diseases.
- The exact function of PrPC is unknown, but cellular localization may be key.
Purpose of the Study:
- To investigate the presence and characteristics of PrPC within brain mitochondria.
- To determine if PrPC localization in mitochondria is associated with disease states.
Main Methods:
- Analysis of brain mitochondria from wild-type and transgenic mice (6-12 weeks old).
- Biochemical assays to assess PrPC processing (N-linked glycans) and localization.
- Protease treatment of purified mitochondria to determine PrPC topology.
Main Results:
- PrPC is present in brain mitochondria of healthy, young mice.
- Mitochondrial PrPC is fully processed and does not require a GPI anchor for localization.
- Protease protection assays indicate PrPC is a transmembrane protein within mitochondria, with C-terminus in the matrix and N-terminus in the intermembrane space.
Conclusions:
- PrPC is found in mitochondria in the absence of disease, aging, mutation, or overexpression.
- The presence of PrPC in mitochondria suggests a novel role in cellular function.
- Further research is warranted to elucidate the impact of mitochondrial PrPC on mitochondrial physiology.
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