Trafficking of PrP<sup>c</sup>to mitochondrial raft-like microdomains during cell apoptosis

Sorice, Maurizio; Mattei, Vincenzo; Tasciotti, Vincenzo; Manganelli, Valeria; Garofalo, Tina; Misasi, Roberta

doi:10.4161/pri.20479

Cited by 25 publications

(21 citation statements)

References 40 publications

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“…Studies using a green fluorescent protein reporter system have suggested that this recycling process may also result in PrP C expression within the Golgi apparatus (Lee et al, 2001; Magalhaes et al, 2002; Nikles et al, 2008). Furthermore, there are reports that PrP C can be present in the nucleus (Gu et al, 2003; Morel et al, 2008; Besnier et al, 2015; Bravard et al, 2015) and in mitochondria (Hachiya et al, 2005; Satoh et al, 2005; Sorice et al, 2012; Faris et al, 2017). Regardless of the different subcellular locations that PrP C can reside, the functional form is believed to be that present on the cell surface.…”

Section: The Cellular Prion Protein and Its Genementioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

156

157

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The prion protein, PrPC, is a small, cell-surface glycoprotein notable primarily for its critical role in pathogenesis of the neurodegenerative disorders known as prion diseases. A hallmark of prion diseases is the conversion of PrPC into an abnormally folded isoform, which provides a template for further pathogenic conversion of PrPC, allowing disease to spread from cell to cell and, in some circumstances, to transfer to a new host. In addition to the putative neurotoxicity caused by the misfolded form(s), loss of normal PrPC function could be an integral part of the neurodegenerative processes and, consequently, significant research efforts have been directed toward determining the physiological functions of PrPC. In this review, we first summarise important aspects of the biochemistry of PrPC before moving on to address the current understanding of the various proposed functions of the protein, including details of the underlying molecular mechanisms potentially involved in these functions. Over years of study, PrPC has been associated with a wide array of different cellular processes and many interacting partners have been suggested. However, recent studies have cast doubt on the previously well-established links between PrPC and processes such as stress-protection, copper homeostasis and neuronal excitability. Instead, the functions best-supported by the current literature include regulation of myelin maintenance and of processes linked to cellular differentiation, including proliferation, adhesion, and control of cell morphology. Intriguing connections have also been made between PrPC and the modulation of circadian rhythm, glucose homeostasis, immune function and cellular iron uptake, all of which warrant further investigation.

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Section: The Cellular Prion Protein and Its Genementioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

156

157

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“…In this respect, we recently identified PrP C , a GPI-anchored glycoprotein, as a new interacting protein component of mitochondrial raft-like microdomains in lymphoblastoid T cells undergoing CD95/Fas-mediated apoptosis. It indicates that raft components can undergo intracellular re-localization via ER-mitochondria associated membranes and microtubular network [79,80]. Hence, we hypothesized that, following CD95/Fas triggering, microtubules could play key roles in the intracellular directional redistribution, as well as in the recruitment to the mitochondrial compartment, of both glycosphingolipids and protein raft components [79].…”

Section: Gd3 Traffic To Mitochondriamentioning

confidence: 99%

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

et al. 2015

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Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies.

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“…Despite their mitochondrial origin, these proteins should not be considered as contaminants of DRMs preparations. Several biochemistry and proteomic studies had already shown the presence of complex I and ATP-synthase subunits in DRMs, [40,41] and Poston showed that Triton X-114-resistant DRMs are also present in mitochondria and contain proteins that facilitate ATP production and export from this organelle [23], compatible with the increasing evidence of the presence of raft-like microdomains in mitochondria [21,42].…”

Section: Proteomicsmentioning

confidence: 63%

Quantitative Proteomic Analysis of Skeletal Muscle Detergent- Resistant Membranes in a Smith-Lemli-Opitz Syndrome Mouse

Cardoso¹,

Vitorino²,

Reguengo³

et al. 2018

Cholesterol - Good, Bad and the Heart

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Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of metabolism affecting the last step of cholesterol biosynthesis. It is characterized by a deficiency of the enzyme 7dehydrocholesterol reductase and accumulation of 7-dehydrocholesterol (7DHC) in cells and body fluids. Given the similarities between 7DHC and cholesterol, 7DHC can be incorporated into cell membranes in lieu of cholesterol. Nevertheless, due to their structural differences and distinct affinity to other membrane components, this substitution alters membrane properties and one can expect to find abnormalities in membrane protein composition. In order to identify differences in membrane proteins that could facilitate our understanding of SLOS physiopathology, we isolated detergent-resistant membranes (DRMs) from the skeletal muscle of Dhcr7 T93M/T93M mice and C57/BL6 controls and performed comparative proteomic analysis using iTRAQ for peptide quantification. A total of 133 proteins were identified in the DRM fraction: 17 (13%) proteins demonstrated increased expression in SLOS mice, whereas, 21 (16%) showed decreased expression. Characterization of functional point of view and bioenergetics pathway and transmembrane transport responded to the major differences between the two groups of animals.

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Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis

Cited by 25 publications

References 40 publications

Physiological Functions of the Cellular Prion Protein

Physiological Functions of the Cellular Prion Protein

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Quantitative Proteomic Analysis of Skeletal Muscle Detergent- Resistant Membranes in a Smith-Lemli-Opitz Syndrome Mouse

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Trafficking of PrPcto mitochondrial raft-like microdomains during cell apoptosis

Cited by 25 publications

References 40 publications

Physiological Functions of the Cellular Prion Protein

Physiological Functions of the Cellular Prion Protein

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Quantitative Proteomic Analysis of Skeletal Muscle Detergent- Resistant Membranes in a Smith-Lemli-Opitz Syndrome Mouse

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Product

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Trafficking of PrP^cto mitochondrial raft-like microdomains during cell apoptosis