Helicobacter pylori Infection Modulates Host Cell Metabolism through VacA-Dependent Inhibition of mTORC1

被引：93

作者：

Kim, Ik-Jung ^{[1
]}

Lee, Jeongmin ^{[2
]}

Oh, Seung J. ^{[2
]}

Yoon, Mee-Sup ^{[3
,7
]}

Jang, Sung-Soo ^{[4
]}

Holland, Robin L. ^{[5
]}

Reno, Michael L. ^{[1
]}

Hamad, Mohammed N. ^{[1
]}

Maeda, Tatsuya ^{[8
]}

Chung, Hee Jung ^{[4
]}

Chen, Jie ^{[3
]}

Blanke, Steven R. ^{[1
,6
]}

机构：

[1] Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA

[2] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA

[3] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA

[4] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA

[5] Univ Illinois, Dept Pathobiol, Urbana, IL 61801 USA

[6] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA

[7] Gachon Univ, Sch Med, Dept Mol Med, Incheon 406840, South Korea

[8] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan

来源：

CELL HOST & MICROBE | 2018年 / 23卷 / 05期

关键词：

GASTRIC EPITHELIAL-CELLS; PYLORI VACUOLATING TOXIN; CYTOCHROME-C RELEASE; AMINO-ACIDS; CYTOTOXIN PRODUCTION; AUTOPHAGY; MITOCHONDRIA; INFECTION; PATHWAY; TARGETS;

D O I：

10.1016/j.chom.2018.04.006

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

Helicobacter pylori (Hp) vacuolating cytotoxin (VacA) is a bacterial exotoxin that enters host cells and induces mitochondrial dysfunction. However, the extent to which VacA-dependent mitochondria! perturbations affect overall cellular metabolism is poorly understood. We report that VacA perturbations in mitochondria are linked to alterations in cellular amino acid homeostasis, which results in the inhibition of mammalian target of rapamycin complex 1 (mTORC1) and subsequent autophagy. mTORC1, which regulates cellular metabolism during nutrient stress, is inhibited during Hp infection by a VacA-dependent mechanism. This VacA-dependent inhibition of mTORC1 signaling is linked to the dissociation of mTORC1 from the lysosomal surface and results in activation of cellular autophagy through the Unc 51-like kinase 1 (U1k1) complex. VacA intoxication results in reduced cellular amino acids, and bolstering amino acid pools prevents VacA-mediated mTORC1 inhibition. Overall, these studies support a model that Hp modulate host cell metabolism through the action of VacA at mitochondria.

引用

页码：583 / +

页数：19

共 59 条

[1]

The role of mitochondria in cellular defense against microbial infection [J].