Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0075625
Title: Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
Authors: Lai D.
Tan C.L.
Gunaratne J. 
Quek L.S.
Nei W.
Thierry F.
Bellanger S.
Keywords: hypoxia inducible factor 1alpha
membrane protein
protein E2
reactive oxygen metabolite
unclassified drug
virus protein
apoptosis
article
cell culture
cell fractionation
cell isolation
cell metabolism
cell nucleus
controlled study
cytoplasm
electron microscopy
flow cytometry
genetic transfection
glycolysis
host cell
human
human cell
Human papillomavirus type 18
immunofluorescence
immunohistochemistry
immunoprecipitation
keratinocyte
mass spectrometry
mitochondrial membrane
nonhuman
papillomavirus infection
protein localization
respiratory chain
Western blotting
Apoptosis
Cell Line, Tumor
Cell Nucleus
Cytoplasm
Glycolysis
Human papillomavirus 18
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Mitochondria
Mitochondrial Membranes
Oncogene Proteins, Viral
Reactive Oxygen Species
Viral Proteins
Issue Date: 2013
Citation: Lai D., Tan C.L., Gunaratne J., Quek L.S., Nei W., Thierry F., Bellanger S. (2013). Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism. PLoS ONE 8 (9) : e75625. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0075625
Rights: Attribution 4.0 International
Abstract: Papillomavirus E2 proteins are predominantly retained in the nuclei of infected cells, but oncogenic (high-risk) HPV-18 and 16 E2 can shuttle between the host nucleus and cytoplasm. We show here that cytoplasmic HPV-18 E2 localizes to mitochondrial membranes, and independent mass spectrometry analyses of the E2 interactome revealed association to the inner mitochondrial membrane including components of the respiratory chain. Mitochondrial E2 association modifies the cristae morphology when analyzed by electron microscopy and increases production of mitochondrial ROS. This ROS release does not induce apoptosis, but instead correlates with stabilization of HIF-1α and increased glycolysis. These mitochondrial functions are not shared by the non-oncogenic (low-risk) HPV-6 E2 protein, suggesting that modification of cellular metabolism by high-risk HPV E2 proteins could play a role in carcinogenesis by inducing the Warburg effect. © 2013 Lai et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161465
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0075625
Rights: Attribution 4.0 International
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