scholarly journals Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 621
Author(s):  
Francesca De Falco ◽  
Ivan Gentile ◽  
Pellegrino Cerino ◽  
Anna Cutarelli ◽  
Cornel Catoi ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Embryonic Stem ◽  
Bovine Papillomavirus ◽  
Urothelial Cells ◽  
Inner Mitochondrial Membrane ◽  
Transmission Electron ◽  
Mitochondrial Fractions ◽  
E5 Oncoprotein ◽  
Functional Complex ◽  
Transcription Factor Eb

Prohibitin 2 (PHB2), an inner mitochondrial membrane (IMM) protein, has recently been identified as a novel receptor involved in parkin-mediated mitophagy. In the field of veterinary medicine, the role of PHB2 in parkin-mediated mitophagy was described, for the first time, in urothelial cells of cattle, naturally infected with bovine papillomavirus (BPV). The BPV2 and BPV13 E5 oncoprotein, responsible for abortive infections in urothelial cells, was detected by RT-PCR. Severe ultrastructural abnormalities of the inner mitochondrial membrane were detected using transmission electron microscopy. PHB2 formed a functional complex with PHB1. PHB2 was significantly overexpressed in mitochondrial fractions from urothelial mucosa samples taken from cattle harbouring BPV infection. PHB2 overexpression could be attributed to mitochondrial dysfunction, as its expression levels in the cytosolic, microsomal, and nuclear fractions were seen to be unmodified. Immunoprecipitation studies revealed the interaction between PHB2 and phosphorylated forms of both PINK1 and parkin. Furthermore, PHB2 interacted with LC3-II, a marker of autophagosomal membranes and autophagy receptors, such as p62 and optineurin. PHB2 was shown to interact with transcription factor EB (TFEB), which is activated following parkin-mediated mitophagy, and embryonic stem cell-expressed Ras (ERAS), a constitutive protein coded by ERas. Western blot analysis revealed a significant overexpression of unphosphorylated TFEB in mitochondrial and nuclear fractions from urothelial mucosa samples from cattle suffering from BPV infection. Finally, PHB2 interacted with ERAS, believed to be involved in mitophagosome maturation. Taken together, the molecular and ultrastructural findings of this study suggested that BPV infection is responsible for parkin-dependent mitophagy, in the pathway of which PHB2 plays a crucial role.

scholarly journals Alignment of sarcoplasmic reticulum-mitochondrial junctions with mitochondrial contact points

2011 ◽  
Vol 301 (5) ◽  
pp. H1907-H1915 ◽  
Author(s):  
Cecília García-Pérez ◽  
Timothy G. Schneider ◽  
György Hajnóczky ◽  
György Csordás
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Mitochondrial Membrane ◽  
Inner Mitochondrial Membrane ◽  
Mitofusin 2 ◽  
Atp Production ◽  
Contact Points ◽  
Transmission Electron

Propagation of ryanodine receptor (RyR2)-derived Ca2+ signals to the mitochondrial matrix supports oxidative ATP production or facilitates mitochondrial apoptosis in cardiac muscle. Ca2+ transfer likely occurs locally at focal associations of the sarcoplasmic reticulum (SR) and mitochondria, which are secured by tethers. The outer mitochondrial membrane and inner mitochondrial membrane (OMM and IMM, respectively) also form tight focal contacts (contact points) that are enriched in voltage-dependent anion channels, the gates of OMM for Ca2+. Contact points could offer the shortest Ca2+ transfer route to the matrix; however, their alignment with the SR-OMM associations remains unclear. Here, in rat heart we have studied the distribution of mitochondria-associated SR in submitochondrial membrane fractions and evaluated the colocalization of SR-OMM associations with contact points using transmission electron microscopy. In a sucrose gradient designed for OMM purification, biochemical assays revealed lighter fractions enriched in OMM only and heavier fractions containing OMM, IMM, and SR markers. Pure OMM fractions were enriched in mitofusin 2, an ∼80 kDa mitochondrial fusion protein and SR-mitochondrial tether candidate, whereas in fractions of OMM + IMM + SR, a lighter (∼50 kDa) band detected by antibodies raised against the NH2 terminus of mitofusin 2 was dominating. Transmission electron microscopy revealed mandatory presence of contact points at the junctional SR-mitochondrial interface versus a random presence along matching SR-free OMM segments. For each SR-mitochondrial junction at least one tether was attached to contact points. These data establish the contact points as anchorage sites for the SR-mitochondrial physical coupling. Close coupling of the SR, OMM, and IMM is likely to provide a favorable spatial arrangement for local ryanodine receptor-mitochondrial Ca2+ signaling.

scholarly journals Bovine Papillomavirus Type 2 Infection Associated with Papillomatosis of the Amniotic Membrane in Water Buffaloes (Bubalus bubalis)

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 262 ◽  
Author(s):  
Valeria Russo ◽  
Franco Roperto ◽  
Davide De Biase ◽  
Pellegrino Cerino ◽  
Chiara Urraro ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Amniotic Membrane ◽  
Squamous Metaplasia ◽  
Bubalus Bubalis ◽  
Productive Infection ◽  
Bovine Papillomavirus ◽  
Water Buffaloes ◽  
E5 Oncoprotein ◽  
Functional Complex

Multiple papillomatous nodules were observed scattered over the amniotic membrane in six water buffaloes that had recently aborted. Grossly, some of the nodules had multiple villous projections while others appeared as single prominent conical or cylindrical horns. Histology revealed folded hyperplastic and hyperkeratotic epithelium supported by a narrow fibro-vascular stalk. Using PCR, sequences of the bovine Deltapapillomavirus type 2 (BPV-2) E5 gene were amplified from the amniotic papillomas. Furthermore, expression of the E5 gene was detected using reverse transcription (RT)-PCR. Western blotting revealed BPV-2 E5 oncoprotein as well as L1 protein, suggesting both abortive and productive infection. Additionally, a functional complex composed of BPV-2 E5 oncoprotein and the phosphorylated PDGFβR was detected, which is consistent with the activation of PDGFβR by the interaction with BPV-2 E5 oncoprotein. These results demonstrate that BPV-2 can infect the amnion of water buffaloes and suggest that this infection may cause proliferation of the epithelial cells of the amnion. While the precise pathogenesis in uncertain, it is possible that BPV-2 infection of stratified squamous epithelial cells within squamous metaplasia foci and/or amniotic plaques could lead to papilloma formation. Papillomavirus-associated amniotic papillomas have not previously been reported in any species, including humans.

Modulation of the calcium-activated BK-channel of the inner mitochondrial membrane by hypoxia

2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
D Siemen ◽  
Y Cheng ◽  
X Gu ◽  
P Bednarczyk ◽  
GG Haddad ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Bk Channel ◽  
Inner Mitochondrial Membrane

The Efects of Spaceflight on Mitochondria in Human Lymphocytes (Jurkat).

1999 ◽  
Vol 5 (S2) ◽  
pp. 1118-1119
Author(s):  
Heide Schatten ◽  
Marian Lewis
Keyword(s):  
Mitochondrial Membrane ◽  
Space Shuttle ◽  
Human Lymphocytes ◽  
Jurkat Cells ◽  
Apoptotic Bodies ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Alterations ◽  
Mitochondrial Volume ◽  
Number Of Cells ◽  
Related Increase

Spaceflight induced mitochondrial alterations have been reported for muscle and may be associated with altered physiological functions in space. Mitochondrial alterations are also indicative of preapoptotic events which are seen in greater amounts in cells exposed to spaceflight when compared with cells cultured at 1 g. Preapoptotic mitochondrial changes include alterations of processes at the inner mitochondrial membrane and can result in changes in mitochondrial volume. Higher amounts of oxidative stress during space flight may be one of the causes for changes which lead to apoptosis. Jurkat cells flown on the STS-76 space shuttle mission showed an increase in the number of cells with apoptotic bodies early in the mission and a time-dependent, microgravity-related increase in the Fas/APO-1 cell death factor. Here we investigated the morphology of mitochondria in Jurkat cells exposed to spaceflight during the STS-76 mission.

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