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Chlamydia trachomatis Prevents Apoptosis Via Activation of PDPK1-MYC and Enhanced Mitochondrial Binding of Hexokinase II
- Source :
- EBioMedicine, EBioMedicine, Vol 23, Iss C, Pp 100-110 (2017)
- Publication Year :
- 2017
-
Abstract
- The intracellular human bacterial pathogen Chlamydia trachomatis pursues effective strategies to protect infected cells against death-inducing stimuli. Here, we show that Chlamydia trachomatis infection evokes 3-phosphoinositide-dependent protein kinase-1 (PDPK1) signaling to ensure the completion of its developmental cycle, further leading to the phosphorylation and stabilization of MYC. Using biochemical approaches and imaging we demonstrate that Chlamydia-induced PDPK1-MYC signaling induces host hexokinase II (HKII), which becomes enriched and translocated to the mitochondria. Strikingly, preventing the HKII interaction with mitochondria using exogenous peptides triggers apoptosis of infected cells as does inhibiting either PDPK1 or MYC, which also disrupts intracellular development of Chlamydia trachomatis. These findings identify a previously unknown pathway activated by Chlamydia infection, which exhibits pro-carcinogenic features. Targeting the PDPK1-MYC-HKII-axis may provide a strategy to overcome therapeutic resistance of infection.<br />Highlights • MYC oncogene expression is induced and stabilized in Chlamydia-infected cells via activation of PDPK1. • Activation of the PDPK1-MYC axis enhances hexokinase II expression. • HKII-mitochondria association prevents apoptosis to support chlamydial growth. Activation of oncogenes promotes cell survival and metabolic reprogramming. Intracellular pathogens target oncogenes to exploit cellular machineries and inhibit apoptosis. Al-Zeer et al. now highlight the role of the oncogene MYC for inducing hexokinase II activation during Chlamydia infection, linking cell survival to energy metabolism.
- Subjects :
- 0301 basic medicine
Cancer Research
lcsh:Medicine
Chlamydia trachomatis
Apoptosis
MYC
Mitochondrion
medicine.disease_cause
PDPK1
TNF-α, tumor necrosis factor-α
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Multiplicity of infection
Hexokinase
Phosphorylation
Chlamydia
MOI, multiplicity of infection
EB, elementary body
HKII, hexokinase II
lcsh:R5-920
biology
PARP, poly-(ADP-ribose) polymerase
PI3K, phosphatidylinositol 3-kinase
General Medicine
Immunohistochemistry
Mitochondria
CTL2, Chlamydia trachomatis L2
030220 oncology & carcinogenesis
Host-Pathogen Interactions
VDAC, voltage-dependent anion channel
lcsh:Medicine (General)
Intracellular
Research Paper
Voltage-dependent anion channel
General Biochemistry, Genetics and Molecular Biology
3-Phosphoinositide-Dependent Protein Kinases
Proto-Oncogene Proteins c-myc
03 medical and health sciences
medicine
Humans
RB, reticulate bodies
PI3K/AKT/mTOR pathway
Host-pathogen interaction
p.i., post-infection
lcsh:R
Chlamydia Infections
medicine.disease
Molecular biology
Enzyme Activation
030104 developmental biology
Metabolism
Commentary
biology.protein
Warburg effect
HeLa Cells
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- EBioMedicine, EBioMedicine, Vol 23, Iss C, Pp 100-110 (2017)
- Accession number :
- edsair.doi.dedup.....98cabe11126c2c499fce502e90e7add2