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Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism

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 analys...

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Autores principales: Lai, Deborah, Tan, Chye Ling, Gunaratne, Jayantha, Quek, Ling Shih, Nei, Wenlong, Thierry, Françoise, Bellanger, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782431/
https://www.ncbi.nlm.nih.gov/pubmed/24086592
http://dx.doi.org/10.1371/journal.pone.0075625
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author Lai, Deborah
Tan, Chye Ling
Gunaratne, Jayantha
Quek, Ling Shih
Nei, Wenlong
Thierry, Françoise
Bellanger, Sophie
author_facet Lai, Deborah
Tan, Chye Ling
Gunaratne, Jayantha
Quek, Ling Shih
Nei, Wenlong
Thierry, Françoise
Bellanger, Sophie
author_sort Lai, Deborah
collection PubMed
description 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.
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spelling pubmed-37824312013-10-01 Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism Lai, Deborah Tan, Chye Ling Gunaratne, Jayantha Quek, Ling Shih Nei, Wenlong Thierry, Françoise Bellanger, Sophie PLoS One Research Article 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. Public Library of Science 2013-09-24 /pmc/articles/PMC3782431/ /pubmed/24086592 http://dx.doi.org/10.1371/journal.pone.0075625 Text en © 2013 Lai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lai, Deborah
Tan, Chye Ling
Gunaratne, Jayantha
Quek, Ling Shih
Nei, Wenlong
Thierry, Françoise
Bellanger, Sophie
Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
title Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
title_full Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
title_fullStr Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
title_full_unstemmed Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
title_short Localization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
title_sort localization of hpv-18 e2 at mitochondrial membranes induces ros release and modulates host cell metabolism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782431/
https://www.ncbi.nlm.nih.gov/pubmed/24086592
http://dx.doi.org/10.1371/journal.pone.0075625
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