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PMID:24086592

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Citation

Lai, D, Tan, CL, Gunaratne, J, Quek, LS, Nei, W, Thierry, F and Bellanger, S (2013) Localization of HPV-18 E2 at mitochondrial membranes induces ROS release and modulates host cell metabolism. PLoS ONE 8:e75625

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.

Links

PubMed PMC3782431 Online version:10.1371/journal.pone.0075625

Keywords

Apoptosis/physiology; Cell Line, Tumor; Cell Nucleus/metabolism; Cell Nucleus/virology; Cytoplasm/metabolism; Cytoplasm/virology; Glycolysis/physiology; Human papillomavirus 18/metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Mitochondria/metabolism; Mitochondria/virology; Mitochondrial Membranes/metabolism; Mitochondrial Membranes/virology; Oncogene Proteins, Viral/metabolism; Reactive Oxygen Species/metabolism; Viral Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HPV18:VE2

GO:0044191: host cell mitochondrial membrane

ECO:0000314:

C

Figure 3: "HPV-18 E2 localizes to mitochondrial membranes" Regulatory protein E2 Human papillomavirus type 18

complete
CACAO 12867

HPV18:VE2

GO:0044193: host cell mitochondrial outer membrane

ECO:0000314:

C

Mass spec analyses revealed association of E2 with outer mitochondrial membrane, as seen on FIG 2 and FIG 3. Regulatory protein E2 Human papillomavirus type 18

complete
CACAO 12868

Notes

See also

References

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