Open AccessLocalization of HPV-18 E2 at Mitochondrial Membranes Induces ROS Release and Modulates Host Cell Metabolism
Author(s) -
Deborah Lai,
Chew-Lim Tan,
Jayantha Gunaratne,
Ling Shih Quek,
Wen Long Nei,
Françoise Thierry,
Sophie Bellanger
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0075625
Subject(s) - microbiology and biotechnology , mitochondrion , cytoplasm , mitochondrial carrier , biology , warburg effect , prohibitin , inner mitochondrial membrane , mitochondrial fusion , cell , apoptosis , carcinogenesis , mitochondrial dna , chemistry , glycolysis , metabolism , biochemistry , bacterial outer membrane , gene , escherichia coli
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.